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+Glycine
-Amino-Levolinic Acid (ALA)
Porphobilinogen
Pre-Uro-Porphyrinogen
Heme +Fe
Proto-Porphyrin
Co-Pro-Porphyrinogen
Uroporphyrinogen III
ALA SYNTHETASE(Regulated Step)ALA
Mitochondria
Cytoplasm
OAA Citrate
cis-aconitate
Isocitrate
-KG
Succinyl-CoA
Succinate
Fumarate
Malate
GTP + CoA
FADH2
NADH
I-DH = ADP (low E state)
I-DH = ATP & NADH
Succinyl-CoA
NADH
ATP
CO2 + NADH
ISOCITRATE-DH
KG-DH
CITRATE
SYNTHASE
ATP
Acetyl-CoA
NADH
Acetyl-CoA
PDH
ATP
CO2 + NADH
Acetyl-CoA
CO2 + ATP
Mg
HIGH
ATP + Acetyl-CoA
State favors the
PC Reaction > PDH Rxn
in the liver
Irreversable, important in Regulation
AKG-DH
Citrate Synthase
Pyrivate Kinase
PFK
Hexo/Glucokinase
Glutamate DerivativesGlycineArginine
Histidine
Prolone
Aceto-Acetyl-CoA
Leucine
Lysine
Tryptophan
Tyrosine
Isoleucine
GABA: Via Glutamate Decarboxylation
Glutamate
ATP & NH4
Glutamine
+ NADPH + H Glutamate y-Semialdehyde Spontaneous Proline-5-carboxylateCyclicization
+ NADPH + H Proline
+ Glutamate
Ornithine + KG
UREA CYCLE
Arginine
KG + NH4 + NADPH + H
TRANSAMINASES
KetoAcid + Glu
All AAs + aKG
Asp + aKG Glu + OAA
Asn + Glu Gln + AspATP
Glutamate DerivativesReduction of AKG to Glutamate
Decarboxylation of Glutamtate to GABA
Amination of Glutamate to Glutimine
Reduction of Glutamte to Glutamate to Glutamate Semialdehyde
Tranglutamination of Glutamate Semialdehyde to Ornithine
Ornithine can enter the UREA CYCLE and produce Arginine
Spontansouse Cyclization of Glutamate Semialdehyde to Proline 5 Carboxylate
Reduction of Proline 5 Carboxylate to Proline
Phenylalanine / Tyrosine
Iso, Met, Thr, Val
Ala, Cys, Gly, Ser, Thr
Essential AAs
PVT TIM HALL
Phe
Val
Thr
Trp
Ile
Met
His
Arg
Leu
Lyse
Non-Essential AAs
3PG --> Ser Cysteine Gly
Pyruvate --> Ala
AKG --> Glu, Arg, Pro
Phe --> Tyr
OAA --> Asp --> Asn
Non-Essential AAs
Ser, Cys, Gly
Ala
Asp, Asn
Glu, Arg, Pro
Tyr
Glucose
G6P
F6P
F1,6DP
G3P #5 TPI DHAP
1,3DPG
3PG
2PG
PEP
Pyruvate
#1 HEXOKINASE
#2 PHOSPHO-GLUCOSE ISOMERASE
#3 PFK
#4 ALDOLASE
#6 GLYCERALDEHYDE-3-PHOSPHATE DH
#7 PHOSPHO-GLYCERATE KINASE
#8 PHOSPHO-GLYCERO-MUTASE
#9 ENOLASE
#10 PYRUVATE KINASE
1 ATP Used (Net = -1)
ATP
ADP
1 ATP Produced x2 = 2ATP (net = +2ATP)
NAD
NADH
Hb
Met-HbMETHEMOGLOBIN REDUCTASE
23BPG DIHYDRO-GLYCERO-MUTASE
23BPG DPG PHOSPHATASE
+ NADH LACTATE-DH Lactate + NAD
PK = F1,6BP activate
PK = Alanine + cAMP Glucagon inhibit favoring Gluconeogensis
Citrate Inhibits PFK
favoring Gluconeogensis
1 ATP Used (Net = -2)
1NADH Produced x2 = 2NADH
LDH recycles NAD under aneurobic condition
so we can continue Glycolysis and produce 2ATP/Glucose
1 ATP Produced x2 = 2ATP) (net = 0ATP)
Fructose
F1P
DHAP + Glyceraldehyde + NADH Glycerol + NAD
G3P
TRIOSE KINASE
FRUCTOKINASE
ALDOLASE B
G3PATP + Glycerol
G3P + ADP GLYCEROL KINASE
G3P SerineTHF N5N10-methyleneTHF
Glycine CO2 + NH4
N5N10-M-THF + dUMP THYMIDILATE SYNTHASE DHF + dTMP
dTTP
N5N10-M-THF + Glycine Serine + THF DIHYDROFOLATE REDUCTASE DHF
*MTX, TMPT
+ Acetyl-CoA + 2NADPH HMG-CoA Reductase Mevalonic Acid + NADP+
IPP + DPP
GPP + IPP
FPP + FPP
Squalene
Cholesterol + ErgosterolHormones
Bile Acids
VitimainD
~Sugar
~amide~Carbon Chain
C3|
C2
|C1
~Carbon ChainOH~Glycophinolipids
NH2~
OH~
C3|
C2
|C1
~Carbon ChainOH~Sphingosine
~OH
~amide
OH~~Carbon Chain
C3|
C2
|C1
~Carbon ChainCeramides
~amide
OH~
~OPO3
~Carbon Chain
C3|
C2
|C1 ~Choline
~Carbon ChainSphingomyelins
~ester
~OPO3
~Carbon Chain
C3|
C2
|C1
Glycerophosphlipids
~ester
~Choline
~Carbon Chain
C3|
C2
|C1OH~
OH~OH~
THF N5N10-methyleneTHF+H2O
Homocysteine + Serine + B6 Cystathione Cysteine Methionine
via SAM CH3
CH3-THF
Vit-B12THF
CYSTATHIONE
SYTHASE
METHIONINE
SYTHASE
Glucose
Pyruvate
Alanine (NH3)-KetoGlu
Glu(NH3)-Ketoacids
Amino Acids (NH3)
MUSCLE
Pyruvate Gluconeogenesis
Alanine (NH3)
Transamination
Glutamate (NH3)
aKG
to UREA Cycle
NH4
Oxidative Deamination
LIVERGLUCOSE
ALANINE CYCLE
to Muscle
Glucose
PYRUVATE
CARBOXYLASE
ATP + CO2
ADP + pi
Malonyl-CoA
NUCLEOTIDE
PRECURSOR
FumerateOxidative Deamination of Glu
GLUTAMATE-DH
NADH
NH4
NAD
To Urea
Cycle
Phenylalanine
(Catecolamines, Melanin, Thyroxine)
TCA
(Niacin = B3, Serotonin = 5HT, Melatonin)
Creatine, Urea, NO
pi +
G6-PHOSPHATASE
H2O +
pi +
F1,6,BISPHOSPHATASE
H2O +
CO2 + PEP
PEP-CARBOXYLASE
OAA
MALATE-DH
Malate
NADH
NAD MALATE-DH
GDP
GTP
F2,6BP AMP F1,6BP
Glucagon [cAMP] Glucagon/cAMP activate F16BPase
(F26Bisphosphatase)
PFK = F6P, AMP, F26BP
PFK = ATP, Citrate
[cAMP] Glucagon(F26Bisphosphatase)
Glucagon/cAMP inhibit PFK
Phe PHENALALANINE HYDROXYLASE Tyr TYROSINASE Melanin
Homogentisate
HOMOGENTISIC ACID OXIDASE
fumarylacetacetate
fumarate
TCA
TERTRAHYDROBIOPTERIN
*PKU here
*Alkaptonuria here
*Albinism here
NH4 + CO2
UREA
CYCLE
Argino-Succinate
Arginine
Ornithine
Citrulline
UreaH2O
NH2
CO OPO3
Carbamoyl Phosphate
ORNITHINE
TRANSCARBAMYLASE
Ornithine + Carbomyl Phosphatate Citrulline
Fumerate
Aspartate
Liver MitochondriaCytoplasm
OT
G6P
G6P-DH
6-Phospho-gluconolactone
GLUCONOLACTONASE
6-Phospho-gluconate
6PHOSPHO-GLUCONATE-DH
R5P
( xylulose )
R5P-ISOMERASE R5P-EPIMERASE
R5P
TRANSKETOLASE
TRANSALDOLASE
TRANSKETOLASE
G3P + F6P
oxidative
phase
NADP + 2GSH
NADPH + GS-SG
2GSH + HOOH
GS-SG + 2H2OScavangingGlutathion Reductase
NADPH
NADP
non-oxidative
phase
PPP/HMP Shunt
TGalactose + ATP GALACTOKINASE Gal-1P ADPGalactitol
ALDOSE REDUCTASE
URIDYL0TRANSFERASE
GAL-1P
UDP-GAL-4-EPIMERASE
UDP-Glucose UDP-Gal
Glu-1P PHOSPHOGLUCOMUTASE
GLUCOSE 1P
URIDYL TRANSFERASE4-Glu-1-OPPiO-Uridine
(4OH-Glu-1)~(4-Glu-1)~(4-Glu-1~OH) (Reducing End with a free OH)Non-reducingEnd (4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1~OH) (Reducing End with a free OH)Non-reducingEnd
6OH
(Reducing End
with a free OH)
GLYCOGEN SYTHASE + (4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1~OH) (Reducing End with a free OH)Non-reducingEnd +
(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1~OH)
O6
(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1~ Non-reducingEnd
Non-reducing
End
PHOSPHORYLASE
G1P
PHOSPHOGLUCOMUTASE
G6P
(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1~OH
O6
(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1~ Non-reducingEnd
Non-reducing
End
(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-(4-Glu-1)~(4-Glu-1)~(4-Glu-1)
O6
HO~4-Glu-1~
(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-Glu-1)~(4-(4-Glu-1)~(4-Glu-1)~(4-Glu-1) + Glucose
DEBRANCHING ENZYME (Tranferase Activity)
The glucose in -(1,6)-linkage at the branch is then removed by the action of glucosidase.
This glucose residue is uncharged
The transferase activity removes the terminal 3 glucose residues of one branch
and attaches them to a free C-4 end of a second branch.
DEBRANCHING ENZYME (GLUCOSIDASE ACTIVITY
DEBRANCHING ENZYME
Aminoglucotransferase (branching enzyme)
(+ Glygogen -1)
TYPE 1 GLYCOGEN STORAGE DISEASE = Von Gierkes disease
df @ Glucose-6- phosphatase @ Liver and kidney.
Severe fasting hypoglycemia
Lactic acidosis. Hepatomegaly (100%)
Short stature (90%). Delayed puberty.
Bleeding diathesis (especially epistaxis).
Hepatic adenomas (75%)
Renal failure and gout in 20s and 30s.
TYPE 2 GSD = Pompes disease
df @ -1,4-glucosidase (acid maltase) @ All organs (enzyme is in lysosomes).
Progressive muscle weakness.
Breathing and feeding difficulties.
Hyporeflexia or areflexia due to glycogen accumulation in spinal motor neurons.
Cardiomegaly leading to congestive heart failure
death before the age of 2
TYPE 3 GSD = Coris disease
df @ Debranching enzyme (-1,6-glucosidase) @ Muscle and liver.
Similar to type I without lactic acidosis
Hypoglycemia
Hepatomegaly
Delayed (ultimately normal) growth.
Symptoms usually regress in adulthood
Type 5 GSD = McArdles disease
df @ Myophosphorylase @ Muscle.
Muscle weakness and cramps after exercise
Myoglobinuria (burgundy urine) after exercise
OVERVIEW OF METABOLISM
TRIOSPHOSPHATE ISOMERASE
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