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LEHNINGER PRINCIPLES OF BIOCHEMISTRY
Fifth Edition
David L Nelson and Michael M Cox
copy 2008 W H Freeman and Company
CHAPTER 21 Lipid Biosynthesis
Biosynthesis of TG phospholipid cholesterol PGs amp LTs
Lipid Biosynthesis
Lipid의 역할
① 저장 E
② 세포막의 구성성분
③ 색소 보조인자(VitE) 계면활성제(bile acid)
carrier(dolichol) VtD 유도체 성 Hormone
세포내외 messenger (Eicosanoidphosphatidyl inositol 유도체) 막 단백
anchor( 닻)
지방질의 생합성 반응
E 투입(ATP) NADPH(전자운반체)
1) Malonyl-CoA의 합성
(1) Acetyl-CoA carboxylase
① Biotin carrier protein
② Biotin carboxylase ATP-dependent 반응 rArr CO2를 biotin에 부착시켜 CO2를 활성화
③ Transcarboxylase 활성화된 CO2를 acetyl-CoA에 전하여 malonyl-CoA 생성
(2) Malonyl-CoA 합성
Biotin carrier protein biotin
carboxylase
ADP+Pi
일시적 CO2운반체
transcarboxylase
acetyl-CoA
bull Fatty acid의 생합성
Malonyl-CoA의 active form
간 뇌 신장 유선 지방조직의 cytosol
+ HCO3- malonyl-CoA
ATP
N C O-
O
O O C-CH2-C -O S-CoA
2) Lipid 생성효소
(1) Fatty acid synthase complex
(2) 역할
Acetyl기와 malonyl기를 받아들여 지방산 사슬을 늘리기 위한 축합 반응을 준비
① ACP thioester 결합된 acyl기 운반
② TE 합성된 acyl기 유리
③ KS Acyl기와 malonyl기 축합
④ MAT Malonyl acetyl기 전달
⑤ KR β-keto기 rarr β-hydroxyl기
⑥ DH β-hydroxyacyl-ACP의 H2O제거rArr생성
⑦ ER =환원 포화 acyl-ACP 생성
CH3
C=O
S
CH2
C=O
S
COO-
CO2
Malonyl gr
Acyl Carrier Protein (ACP)
최초의 acyl기
β-ketoacyl -ACP생성효소
(KS)
β-ketoacyl-ACP synthase (KS) malonylacetyl-CoAmdashACP transferase (MAT) β-hydroxyacyl-ACP dehydratase (DH) enoyl-ACP reductase (ER) and β-ketoacyl-ACP reductase (KR) ACP is the acyl carrier protein thioesterase(TE)
FIGURE 21-1 The acetyl-CoA carboxylase reaction
FIGURE 21-2 Addition of two carbons to a growing fatty acyl chain a four-step sequence
FIGURE 21-3 The structure of fatty acid synthase type I systems
porcine fungus
β-ketoacyl-ACP synthase (KS) malonylacetyl-CoAmdashACP transferase (MAT) β-hydroxyacyl-ACP dehydratase (DH) enoyl-ACP reductase (ER) and β-ketoacyl-ACP reductase (KR) ACP is the acyl carrier protein thioesterase(TE)
FIGURE 21-4 The overall process of palmitate synthesis
FIGURE 21-5 Acyl carrier protein (ACP)
FIGURE 21-6 Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 1) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 2) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 3) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 4) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 5) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 6) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 7) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 8) Sequence of events during synthesis of a fatty acid
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
Lipid Biosynthesis
Lipid의 역할
① 저장 E
② 세포막의 구성성분
③ 색소 보조인자(VitE) 계면활성제(bile acid)
carrier(dolichol) VtD 유도체 성 Hormone
세포내외 messenger (Eicosanoidphosphatidyl inositol 유도체) 막 단백
anchor( 닻)
지방질의 생합성 반응
E 투입(ATP) NADPH(전자운반체)
1) Malonyl-CoA의 합성
(1) Acetyl-CoA carboxylase
① Biotin carrier protein
② Biotin carboxylase ATP-dependent 반응 rArr CO2를 biotin에 부착시켜 CO2를 활성화
③ Transcarboxylase 활성화된 CO2를 acetyl-CoA에 전하여 malonyl-CoA 생성
(2) Malonyl-CoA 합성
Biotin carrier protein biotin
carboxylase
ADP+Pi
일시적 CO2운반체
transcarboxylase
acetyl-CoA
bull Fatty acid의 생합성
Malonyl-CoA의 active form
간 뇌 신장 유선 지방조직의 cytosol
+ HCO3- malonyl-CoA
ATP
N C O-
O
O O C-CH2-C -O S-CoA
2) Lipid 생성효소
(1) Fatty acid synthase complex
(2) 역할
Acetyl기와 malonyl기를 받아들여 지방산 사슬을 늘리기 위한 축합 반응을 준비
① ACP thioester 결합된 acyl기 운반
② TE 합성된 acyl기 유리
③ KS Acyl기와 malonyl기 축합
④ MAT Malonyl acetyl기 전달
⑤ KR β-keto기 rarr β-hydroxyl기
⑥ DH β-hydroxyacyl-ACP의 H2O제거rArr생성
⑦ ER =환원 포화 acyl-ACP 생성
CH3
C=O
S
CH2
C=O
S
COO-
CO2
Malonyl gr
Acyl Carrier Protein (ACP)
최초의 acyl기
β-ketoacyl -ACP생성효소
(KS)
β-ketoacyl-ACP synthase (KS) malonylacetyl-CoAmdashACP transferase (MAT) β-hydroxyacyl-ACP dehydratase (DH) enoyl-ACP reductase (ER) and β-ketoacyl-ACP reductase (KR) ACP is the acyl carrier protein thioesterase(TE)
FIGURE 21-1 The acetyl-CoA carboxylase reaction
FIGURE 21-2 Addition of two carbons to a growing fatty acyl chain a four-step sequence
FIGURE 21-3 The structure of fatty acid synthase type I systems
porcine fungus
β-ketoacyl-ACP synthase (KS) malonylacetyl-CoAmdashACP transferase (MAT) β-hydroxyacyl-ACP dehydratase (DH) enoyl-ACP reductase (ER) and β-ketoacyl-ACP reductase (KR) ACP is the acyl carrier protein thioesterase(TE)
FIGURE 21-4 The overall process of palmitate synthesis
FIGURE 21-5 Acyl carrier protein (ACP)
FIGURE 21-6 Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 1) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 2) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 3) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 4) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 5) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 6) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 7) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 8) Sequence of events during synthesis of a fatty acid
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
1) Malonyl-CoA의 합성
(1) Acetyl-CoA carboxylase
① Biotin carrier protein
② Biotin carboxylase ATP-dependent 반응 rArr CO2를 biotin에 부착시켜 CO2를 활성화
③ Transcarboxylase 활성화된 CO2를 acetyl-CoA에 전하여 malonyl-CoA 생성
(2) Malonyl-CoA 합성
Biotin carrier protein biotin
carboxylase
ADP+Pi
일시적 CO2운반체
transcarboxylase
acetyl-CoA
bull Fatty acid의 생합성
Malonyl-CoA의 active form
간 뇌 신장 유선 지방조직의 cytosol
+ HCO3- malonyl-CoA
ATP
N C O-
O
O O C-CH2-C -O S-CoA
2) Lipid 생성효소
(1) Fatty acid synthase complex
(2) 역할
Acetyl기와 malonyl기를 받아들여 지방산 사슬을 늘리기 위한 축합 반응을 준비
① ACP thioester 결합된 acyl기 운반
② TE 합성된 acyl기 유리
③ KS Acyl기와 malonyl기 축합
④ MAT Malonyl acetyl기 전달
⑤ KR β-keto기 rarr β-hydroxyl기
⑥ DH β-hydroxyacyl-ACP의 H2O제거rArr생성
⑦ ER =환원 포화 acyl-ACP 생성
CH3
C=O
S
CH2
C=O
S
COO-
CO2
Malonyl gr
Acyl Carrier Protein (ACP)
최초의 acyl기
β-ketoacyl -ACP생성효소
(KS)
β-ketoacyl-ACP synthase (KS) malonylacetyl-CoAmdashACP transferase (MAT) β-hydroxyacyl-ACP dehydratase (DH) enoyl-ACP reductase (ER) and β-ketoacyl-ACP reductase (KR) ACP is the acyl carrier protein thioesterase(TE)
FIGURE 21-1 The acetyl-CoA carboxylase reaction
FIGURE 21-2 Addition of two carbons to a growing fatty acyl chain a four-step sequence
FIGURE 21-3 The structure of fatty acid synthase type I systems
porcine fungus
β-ketoacyl-ACP synthase (KS) malonylacetyl-CoAmdashACP transferase (MAT) β-hydroxyacyl-ACP dehydratase (DH) enoyl-ACP reductase (ER) and β-ketoacyl-ACP reductase (KR) ACP is the acyl carrier protein thioesterase(TE)
FIGURE 21-4 The overall process of palmitate synthesis
FIGURE 21-5 Acyl carrier protein (ACP)
FIGURE 21-6 Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 1) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 2) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 3) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 4) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 5) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 6) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 7) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 8) Sequence of events during synthesis of a fatty acid
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
2) Lipid 생성효소
(1) Fatty acid synthase complex
(2) 역할
Acetyl기와 malonyl기를 받아들여 지방산 사슬을 늘리기 위한 축합 반응을 준비
① ACP thioester 결합된 acyl기 운반
② TE 합성된 acyl기 유리
③ KS Acyl기와 malonyl기 축합
④ MAT Malonyl acetyl기 전달
⑤ KR β-keto기 rarr β-hydroxyl기
⑥ DH β-hydroxyacyl-ACP의 H2O제거rArr생성
⑦ ER =환원 포화 acyl-ACP 생성
CH3
C=O
S
CH2
C=O
S
COO-
CO2
Malonyl gr
Acyl Carrier Protein (ACP)
최초의 acyl기
β-ketoacyl -ACP생성효소
(KS)
β-ketoacyl-ACP synthase (KS) malonylacetyl-CoAmdashACP transferase (MAT) β-hydroxyacyl-ACP dehydratase (DH) enoyl-ACP reductase (ER) and β-ketoacyl-ACP reductase (KR) ACP is the acyl carrier protein thioesterase(TE)
FIGURE 21-1 The acetyl-CoA carboxylase reaction
FIGURE 21-2 Addition of two carbons to a growing fatty acyl chain a four-step sequence
FIGURE 21-3 The structure of fatty acid synthase type I systems
porcine fungus
β-ketoacyl-ACP synthase (KS) malonylacetyl-CoAmdashACP transferase (MAT) β-hydroxyacyl-ACP dehydratase (DH) enoyl-ACP reductase (ER) and β-ketoacyl-ACP reductase (KR) ACP is the acyl carrier protein thioesterase(TE)
FIGURE 21-4 The overall process of palmitate synthesis
FIGURE 21-5 Acyl carrier protein (ACP)
FIGURE 21-6 Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 1) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 2) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 3) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 4) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 5) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 6) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 7) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 8) Sequence of events during synthesis of a fatty acid
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-1 The acetyl-CoA carboxylase reaction
FIGURE 21-2 Addition of two carbons to a growing fatty acyl chain a four-step sequence
FIGURE 21-3 The structure of fatty acid synthase type I systems
porcine fungus
β-ketoacyl-ACP synthase (KS) malonylacetyl-CoAmdashACP transferase (MAT) β-hydroxyacyl-ACP dehydratase (DH) enoyl-ACP reductase (ER) and β-ketoacyl-ACP reductase (KR) ACP is the acyl carrier protein thioesterase(TE)
FIGURE 21-4 The overall process of palmitate synthesis
FIGURE 21-5 Acyl carrier protein (ACP)
FIGURE 21-6 Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 1) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 2) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 3) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 4) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 5) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 6) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 7) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 8) Sequence of events during synthesis of a fatty acid
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-2 Addition of two carbons to a growing fatty acyl chain a four-step sequence
FIGURE 21-3 The structure of fatty acid synthase type I systems
porcine fungus
β-ketoacyl-ACP synthase (KS) malonylacetyl-CoAmdashACP transferase (MAT) β-hydroxyacyl-ACP dehydratase (DH) enoyl-ACP reductase (ER) and β-ketoacyl-ACP reductase (KR) ACP is the acyl carrier protein thioesterase(TE)
FIGURE 21-4 The overall process of palmitate synthesis
FIGURE 21-5 Acyl carrier protein (ACP)
FIGURE 21-6 Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 1) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 2) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 3) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 4) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 5) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 6) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 7) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 8) Sequence of events during synthesis of a fatty acid
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-3 The structure of fatty acid synthase type I systems
porcine fungus
β-ketoacyl-ACP synthase (KS) malonylacetyl-CoAmdashACP transferase (MAT) β-hydroxyacyl-ACP dehydratase (DH) enoyl-ACP reductase (ER) and β-ketoacyl-ACP reductase (KR) ACP is the acyl carrier protein thioesterase(TE)
FIGURE 21-4 The overall process of palmitate synthesis
FIGURE 21-5 Acyl carrier protein (ACP)
FIGURE 21-6 Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 1) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 2) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 3) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 4) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 5) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 6) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 7) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 8) Sequence of events during synthesis of a fatty acid
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-4 The overall process of palmitate synthesis
FIGURE 21-5 Acyl carrier protein (ACP)
FIGURE 21-6 Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 1) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 2) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 3) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 4) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 5) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 6) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 7) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 8) Sequence of events during synthesis of a fatty acid
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-5 Acyl carrier protein (ACP)
FIGURE 21-6 Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 1) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 2) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 3) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 4) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 5) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 6) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 7) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 8) Sequence of events during synthesis of a fatty acid
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-6 Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 1) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 2) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 3) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 4) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 5) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 6) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 7) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 8) Sequence of events during synthesis of a fatty acid
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-6 (part 1) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 2) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 3) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 4) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 5) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 6) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 7) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 8) Sequence of events during synthesis of a fatty acid
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-6 (part 2) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 3) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 4) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 5) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 6) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 7) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 8) Sequence of events during synthesis of a fatty acid
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-6 (part 3) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 4) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 5) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 6) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 7) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 8) Sequence of events during synthesis of a fatty acid
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-6 (part 4) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 5) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 6) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 7) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 8) Sequence of events during synthesis of a fatty acid
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-6 (part 5) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 6) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 7) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 8) Sequence of events during synthesis of a fatty acid
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-6 (part 6) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 7) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 8) Sequence of events during synthesis of a fatty acid
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-6 (part 7) Sequence of events during synthesis of a fatty acid
FIGURE 21-6 (part 8) Sequence of events during synthesis of a fatty acid
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-6 (part 8) Sequence of events during synthesis of a fatty acid
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-7 Beginning of the second round of the fatty acid synthesis cycle
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-8 Subcellular localization of lipid metabolism
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-9 Production of NADPH
(c)Isocitrate dehydrogenase
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-10 Shuttle for transfer of acetyl groups from mitochondria to the cytosol
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-11 Regulation of fatty acid synthesis
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-12 Routes of synthesis of other fatty acids
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-13 Electron transfer in the desaturation of fatty acids in vertebrates
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
3)다양한 지방산 생합성의 조절
(1) Palmitate를 전구체로 하는 생합성 ( unsaturation elongation)
eicosatriene
arachidonate
citrate 분해효소
+insulin
Acetyl-CoA carboxylase
-glucagon epinephrine +citrate -palmitoyl-CoA
Palmitate 16 0
palmitoleic acid 161(∆9)
stearate 180 길어진 포화지방산
oleic acid 181(∆9)
linoleic acid 182(∆912)
α-linoleic acid
EPA
γ-linoleic acid
(2) 조절
Citrate acetyl-CoA malonyl-CoA palmitoyl-CoA
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-14 Action of plant desaturases
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
③ aspirin COX의 ser잔기를 acetylation시켜 비가역적으로 불활성화시킴
cf) 50~80mg 복용 혈중 TX만 억제 500mg 복용 동통 억제
iboprofen 경쟁적 억제제
(3) Eicosanoid 합성
① Eicosanoid Paracrine hormone으로 arachidonate에서 유래되었으며
PG TX Leukotriene 3종류가 존재한다
② 합성과정
Arachidonate 204(∆581114)
PGG2 PGH2
COX의 cyclooxygenase
-aspiriniboprofen
COX의 peroxidase 다른 PGs 동통유발 염증물질
Thromboxane 혈관수축 혈소판응집
심장마비 뇌졸중
2O2
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-15a The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-15b The cyclic pathway from arachidonate to prostaglandins and thromboxanes
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-15c The cyclic pathway from arachidonate to prostaglandins and thromboxanes
COX-2ndashspecific cyclooxygenase inhibitors
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-16 The linear pathway from arachidonate to leukotrienes
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
Lipoxygenase LTs lipoxin and resolvins
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
Pro-resolution products of Lipoxygenase
Nature Immunology 6 1191 - 1197 (2005)
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-17 Biosynthesis of phosphatidic acid
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
aa
bull TG의 생합성 지방산의 운명 (저장형태)
① 성장이 왕성 (새로운 막 형성 필요) 인산지방질로 들어감
② 저장지방질 (충분한 음식물 공급 or 성장활발 times) TG
1) TG 저장된 영양분의 가장 높은 E량 (~38kJg 이상)
rArr glycogen으로 저장할 수 있는 양 이상의 당질을 섭취할 때 TG로 지방조직에 저장
Acyl transferase Glycerophospholipid
Acetyl-CoA +insulin +insulin
① 식이성 당질 glucose
식이성 단백질 지방산 TG
ketone body (당질의 TG의 변환을 촉진시킴)
② 당뇨병환자 Insulin의 분비 작용에 결함
rArr glucose를 잘 이용 times 당질aa로부터 지방산 형성 times
rArr 지방산의 산화uarr ketone bodyuarr rArr 체중darr
2) Insulin에 의한 조절
Glucose Dihydroxyacetone
glycerol L-glycerol 3-phosphate Phosphatidate TG
ATP ADP
NADH + H+ NAD+
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-18 Phosphatidic acid in lipid biosynthesis
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-20 The triacylglycerol cycle
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-21 Glyceroneogenesis
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-22a Regulation of glyceroneogenesis
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-22 Regulation of glyceroneogenesis
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-23 Head-group attachment
bull Phospholipid의 생합성
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-24 Two general strategies for forming the phosphodiester bond of phospholipids
원핵세포 진핵세포
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-25 Origin of the polar head groups of phospholipids in E coli
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-26 Synthesis of cardiolipin and phosphatidylinositol in eukaryotes
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-27 The major path from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in all eukaryotes
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-28a Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-28b Pathways for phosphatidylserine and phosphatidylcholine synthesis in mammals
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-29 Summary of the pathways for synthesis of major phospholipids
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-30 Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-30 (part 1) Synthesis of ether lipids and plasmalogens
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-30 (part 2) Synthesis of ether lipids and plasmalogens
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-31 Biosynthesis of sphingolipids
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-31 (part 1) Biosynthesis of sphingolipids
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-31 (part 2) Biosynthesis of sphingolipids
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
bull Cholesterol steroid isoprenoids의 생합성 1) Cholesterol ① 모든 조직에서 acetyl CoA rarr Cholesterol
② 난황 게 새우 육류에 많다
③ 기능 세포막 구성성분 담즙산의 전구체 steroid H 전구체 vitD의 전구체
2) Cholesterol 합성
① acetate로부터 mevalonate 합성
CoA-SH
thiolase HMG-CoA synthase
O CH3C S-CoA
CoA-SH 2NADPH +2H+
2NADP+
CoA-SH
-Statin Mevastatin Lovastatin +insulin -glucagon
(acetyl CoAtimes3)
② mevalonate로부터 활성형 isoprene으로의 전환
③ squalene 합성 (mevalonate times 6 acetyl-CoA times 18)
rArr mevalonic acid(전구체) demethylallyl pyrophosphate
∆3-isopentenyl pyrophospate
④ cholesterol 합성
acetyl CoA acetoacetyl CoA HMG-CoA mevalonate HMG-CoA reductase
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
3) Cholesterol의 운명 ① 담즙 중의 cholesterol
② cholesterol ester Chol CE ACAT
4) 지방질의 운반 ldquoLipoproteinrdquo
① Chylomicron ni TG(≧90) 다량함유 식이성 TG 운반 (장rarr조직)
② VLDL 내인성 TG 운반 간에서 TG를 내놓을 때의 형태
③ HDL 간외조직의 유리 cholesterol을 CE로 간에 운반 rArr동맥경화 억제
ni LCAT (Lecithin-cholesterol acyl transferase)
④ LDL VLDL의 최종대사 형태 말초조직에 cholesterol운반 nichol 함량 높다
rArr동맥경화의 원인
5) Cholesterol이 세포 내로 들어가는 기전
(ACAT Acyl-CoA-cholesterol acyl transferase)
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-32 Origin of the carbon atoms of cholesterol
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-33 Summary of cholesterol biosynthesis
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-34 Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-34 (part 1) Formation of mevalonate from acetyl-CoA
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-34 (part 2) Formation of mevalonate from acetyl-CoA
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-35 Conversion of mevalonate to activated isoprene units
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-36 Formation of squalene
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-38 Synthesis of cholesteryl esters
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
TABLE 21-1 Major Classes of Human Plasma Lipoproteins Some Properties
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-39 Lipoproteins
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-39b Lipoproteins
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
TABLE 21-2 Apolipoproteins of the Human Plasma Lipoproteins
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-40a Lipoproteins and lipid transport
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-40 Lipoproteins and lipid transport
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT)
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-42 Uptake of cholesterol by receptor-mediated endocytosis
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-43 SREBP activation
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
6) Cholesterol 생합성의 조절
β-Hydroxy- β-methylglutayl-CoA
(HMG-CoA)
HMG-CoA reductase
-sterol -glucagon +insulin +고농도의
chol
ACAT (수용체를 통한 Endocytosis)
LDL-chol
HMG-CoA reductase 조절
① sterol 효소의 억제rArr 유전자의 전사억제(SREBP2에 의한)
② glucagon 효소의 인산화 촉진 rArr 불활성화
③ insulin 탈인산화 촉진 rArr 활성화
④ Lovastatin compactin etc mevalonate와 구조적 유사 rArr HMG-CoA의 경쟁적 억제제
Chol
Cholester (저장)
Acetyl-CoA Mevalonate
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
7)Cholesterol의 운명
(1) Steroid hormone 생성
a) Mineralocorticoid rarrrarr aldosterone (신장에서 Na+ Cl- 재흡수 조절)
b) Glucocorticoid 글루코스 신생합성조절 염증반응억제
c) Testosterone rarrrarr estradiol (성H)
(2) Isoprenoids 생성
Vit A E K carotenoid chloropyll(식물색소) 천연고무 lemon 기름
eucalyptus 기름 사향의 방향성분 곤충 변태 hormone dolicol
ubiquinone plastoquinone
(3) Bile acid 생성
5α-reductase dihydro-testosterone
rArr androgen R에 친화력 높음 rarr 탈모
there4 dihydro-testosterone 합성의 inhibitor rArr 대머리 치료제
전립선비대 억제
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-44 Regulation of cholesterol formation balances synthesis with dietary uptake
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
BOX 21-3 FIGURE 1 Statins as inhibitors of HMG-CoA reductase
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-45 Some steroid hormones derived from cholesterol
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-46 Side-chain cleavage in the synthesis of steroid hormones
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
FIGURE 21-47 Overview of isoprenoid biosynthesis
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
Overview of metaboilsm
Glycogenesis Glycogenolysis
F-16-bisphosphatase
F-6-P
Phosphofructokinase
Phosphoenolpyruvate kinase((PEPCK) FOXO1HNF-4
단백질합성
Pyr dehydrogenase
Chol synthesis
HMG-CoA reductase Cholesterol
PPAR αβ
PGC1 α
PKA
cAMP
GProtein
Glucagon Epinephrine
Akt GSK3β
GS
Glycogen 합성
PI3K
IRS
Insulin S70S6K
mTOR
Glut4
Glu
Glu
IR
SREBP-12
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
Glu
Pyr
Pyr
Acetyl CoA
FFA
FFA
Acyl CoA
CPTⅠ
CPTⅡ
Glut4 FATP
TCA cycle
Pyr dehydrogenase
Chol
Ketone body
HMG-CoA β-Oxidation
FA synthesis
ATP
gluconeogenesis
Blood
Cell
Mt
glycolysis
ACS
Chol
Chol synthesis
Acetyl CoA
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
PKA
CREB
PGC-1α
IRS
PI3K
FA합성 Chol합성 Glycogen합성
GSK3β
mTOR
S70S6K
S6protein
FOXO1 HNF-4 PPARα β(δ)
gluconeogenesis β -oxidation
Fasting Diet
Akt
SREBP-12
Glucagon
cAMP
Insulin
CBPp300
AMPK
insulin
insulin