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CHUYN HO PROTEINCHUYN HO PROTEIN

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- Thoi ho protein- Thoi ho acid amin: Thoi ho nit ca acid amin Thoi ho b khung cacbon ca acid amin

- Tng hp acid amin- Chuyn acid amin thnh cc sn phm chuyn bit

Ni dung

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S TNG QUT CHUYN HO PROTID

Protein thc n

Acid amin

Protein c th Cc sn phmcha nit khc

B khung carbon NH4+

Urea

Bi titAcetyl CoA

Pyruvate, sn phmtrung gian chu trnhacid citric

ATP Glucose

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THOI HO PROTEIN

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NHU CU PROTEIN CA C TH

- C th cn 30 60 g/ngy (khong 1g/kg/ngy)- Vai tr:

Tng hp protein cu trc v chc nng: collagen,myosin

Tng hp protein c hot tnh sinh hc: enzym,hormon Tng hp cht c hot tnh sinh hc: histamin,serotonin Cung cp 12% tng nng lng c th ( ng vt n

tht 90%)- Acid amin d tha (t thc n) khng c d tr

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Suy dinh dng nng lng protein:

- Th marasmus: suy kit tng qut do thiu c nng lngv protein.- Th kwashiorkor: c trng bng ph, nng lng nhpvo nhng thiu c cht v lng protein.Thc t thng gp dng trung gian ca 2 th ny.

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NGUN GC ACID AMIN TRONG C TH

AcidAcid aminamin ngoingoi sinhsinh Acid amin ni sinhAcid amin ni sinh

-- T ng vt, thc vtT ng vt, thc vtv vi sinh vt (to,v vi sinh vt (to,

men bia) hp thumen bia) hp thuvo c th qua quvo c th qua qutrnh tiu hotrnh tiu ho

-- TngTng hphp trongtrong ccthth

-- ThuThu phnphn tt proteinproteintt bobo (men(men catepsincatepsincc trongtrong lysosomlysosom,, gygyhinhin tngtng tt tiutiu))

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TIU HO V HP THU PROTEINTiu ho:Proteinase (protease): l cc peptidase thu phn protein thnhpeptid ri thnh acid amin t do:- Endopeptidase: ct cc lin kt peptid bn trong chui: pepsin,trypsin, chymotrypsin, thng c hiu cho acid amin- Exopeptidase: ct lin kt peptid u tn

Aminopeptidase: u N tn Carboxypeptidase: u C tn

Hp thu:Acid amin t do

Nim mc rut non

Tnh mch ca

Gan

M, t bo

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TiuTiu hoho proteinprotein

EnzymEnzym tiutiu haha cc tittit rara didi dngdng tintin enzymenzym((proenzymproenzym)) khngkhng hothot ngng.. KhiKhi cc aa vovolnglng rutrut,, cccc tintin enzymenzym ss cc hothot haha thnhthnhdngdng hothot ngng..

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TiuTiu hoho proteinprotein

EnzymEnzym cc tnhtnh cc hiuhiu,, chch ctct nhngnhng linlin ktkt nhtnhtnhnh

TrypsinTrypsin:: CtCt linlin ktkt peptidpeptid trctrc ArgArg hay Lys.hay Lys.

ChymotrypsinChymotrypsin :: CtCt linlin ktkt peptidpeptid sausau PhePhe,, TrpTrp, Tyr., Tyr.

CtCt chmchm hnhn sausau AsnAsn, His, Met hay, His, Met hay LeuLeu..

ElastaseElastase:: CtCt LKLK peptidpeptid sausau Ala,Ala, GlyGly, Ser,, Ser, hochoc Val.Val.

TiTi ngng tiutiu hoho::

--ProteinProtein cucu ((ngng vtvt)) cc thythy phnphn honhon tonton..

-- ProteinProtein sisi (collagen, keratin)(collagen, keratin) cc tiutiu haha mtmt phnphn..

-- ProteinProtein ngng cccc cc tiutiu haha khngkhng honhon tonton (do(do lplp

cellulose).cellulose).

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VNG LUN CHUYN PROTEINProtein c th

Acid amin

Thoi hoprotein

Ti s dng tng hp protein

Thoi ho

ngi ln, 1-2% tng lng protein c th thoi homi ngy (ch yu t c), to acid amin t do:

- 75-80% c ti s dng tng hp protein mi

- 20-25% to ureaProtein t bo lun c i mi. Qu trnh thoi hoprotein t bo nh enzym catepsin A, B, C tronglysosom ca t bo

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CnCn bngbng nitnit (nitrogen balance)(nitrogen balance)

ngingi trngtrng thnhthnh,, khikhi proteinprotein nnnhnh dodo lnglng proteinprotein tngtng hphp vv proteinproteinthoithoi hoho linlin tctc vv cncn bngbng..

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CN BNG NIT

L s khc bit gia tng lng nit nhp v tnglng nit mt qua phn, nc tiu v m hi.

- Dng: nhp > xut. VD: tr nh ang pht trin, ph

n c thai, ngi bnh hi phc.

- m: nhp < xut. VD: ngi gi, sau phu thut, ungth tin trin, n khng .

Ngi ln bnh thng: nhp = xut

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THOI HO NIT CA ACID AMIN

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SN PHM CA THOI HO NIT NG VT

- ammonia- acid uric- urea

u th ammonia: c xng (Teleostei) (thi nh trao ilin tc vi mi trng nc)

u th acid uric: chim (cn gi nc, gi trng lngthp)

u th urea: ngi (tan nhiu trong nc, khng c)

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Acid -amin Acid -ceto

-Cetoglutarate L-Glutamate

NH3 CO2

Urea

Dng di chuyn ca nit trong d ho acid amin(Sinh tng hp urea)

Chuyn amin

Kh aminoxi ho

Chu trnh urea

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CHUYN AMIN

transaminase

(vitamin B6)

M ng vt: 2 enzyme ph bin nht v hot ng mnh nht lglutamate oxaloacetate transaminase (GOT) v glutamate pyruvatetransaminase (GPT)

-Cetoglutarate

Pyruvate

Alanine

Glutamate

Aspartate

Oxaloacetate

GPT GOT

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C CH PHN NG CHUYN AMIN

Pyridoxal phosphate ng vai tr gi gc amin tm thi cho c cht k tip (acid ceto)(vit B6)

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GPT, GOT

GPT

GOT

GPT=glutamate pyruvate transaminase=ALT=alanine transaminase

GOT=glutamate oxaloacetate transaminase=AST=aspartate transaminase

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GOT, GPT - ng dng lm sng

Xc nh hot transaminase SGOT (AST) vSGPT (ALT) v ch s GOT/GPT (De Ritis) trongcc bnh l tim, gan hay c vnGOT v GPT l cc enzym ni bo, bnh thng

trong huyt thanh < 40 UI/l.Xt nghim trnh v hng cu.Nhi mu c tim: ch yu tng GOT, ch sGOT/GPT > 1, tng gp 2-25 ln, tng sm, cao

nht t 16-48 gi.Vim gan siu vi: tng c GPT v GOT; GPTtng nhiu GOT/GPT < 1, tng gp trm ln,sm trc vng da, tng ko di, chuyn thnh

mn tnh.

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KH AMIN OXY HO

NAD(P)+ NAD(P)H,H+

L-Glutamat -Cetoglutarat

NH3L-Glutamat

dehydrogenase

L-Glutamat dehydrogenase: trung tm ca chuyn ho nit, 75% nit ca protein

n vo chuyn ho theo con ng glutamat

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Amino acid oxidase: m gan, thn

Flavin Flavin+H2

H2O2 O2

H2O

Acid -amin [Acid -imin]

1/2O2

Acid -ceto

H2O

NH3

Amino acid oxidase

Catalase

KH AMIN OXY HO

CHNH2 C=NH C=O

Tch nhm amin ra khi aa di dnh NH3 pH 7,3, duy nht ch c L glutamate dehydrogenase (L.glu. DH) c CoE lNAD+ c kh nng kh amin trc tip ca L. Glutamate mt cch d dng.Gm 2 giai on xy ra ty th * Giai on 1: Kh hydro nh dehydrogenase (DH)

* Giai on 2: Thy phn t pht

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KhKh aminamin oxyoxy hoho

DH

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CHUYN KH AMIN

Hu ht cc transaminase c cng c cht v sn phm (glutamat vcetoglutarate) vi glutamin dehydrogenase phi hp gia phn ngchuyn v kh amin bi tit nit cho tng acid amin.

Qu trnh ny cho thy vai tr trung tm ca glutamat trong kim sotchuyn ho nit.

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LIN QUAN GIA KH AMIN V CHUYNAMIN :

-Cc enzym kh amin oxyha ca cc acid amin hotng yu pH 7,3 ngai tr L glutamate dehydrogenase(L.glu. DH) c CoE l NAD+ .

-Cc enzym Transaminase ca cc acid amin li phbin v hot ng mnh c bit Glutamate aminTransferase.

- Nn hu ht cc aa c kh amin gin tip thng quah thng chuyn amin nh CG lm cht trung gian.

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Chuyn amin Kh amin

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KhKh carboxylcarboxyl toto aminamin

PhPh binbin vi vi sinhsinh vtvt

Cc amin khi ht tc dng, s bkh amin v oxy ho:

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Kh carboxyl to amin

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ChuynChuyn chch NHNH33NHNH33::

NiNi sinhsinh:: KhKh aminamin oxyoxy hoho cccc acidacid aminamin

ThoiThoi hoho basebase nitnit

NgoiNgoi sinhsinh: vi: vi khunkhun cc enzymenzym thuthu phnphn proteinprotein trongtrongrutrut (NH(NH33/TM/TM caca > NH> NH33//tuntun honhon 55--1010 lnln))

GlutaminGlutamin::

KhngKhng cc,, khngkhng mangmang inin tchtch,, nnnn dd vnvn chuynchuynquaqua mngmng..

LL chtcht vnvn chuynchuyn NHNH44++ chch yuyu//mumu

NgunNgun cungcung cpcp nhmnhm aminamin chocho tngtng hphp acidacid aminamin

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TNG HP GLUTAMIN

Mg2+

- Chuyn ch NH3 trong mu. NH3 t do trong mu: 1-2 mg/l

- L c ch kh c NH3 ch yu ca no (to urea khngng vai tr quan trng). Nhng nu NH3 mu cao khng glutamat no tng hp glutamat t -cetoglutarat kitqu cc cht trung gian trong chu trnh acid citric.

Glutamine

synthetase

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VN CHUYN GLUTAMIN TRONG MU

Acid amin

NH3

Glutamin(60-100 mg/l)

NH3 t do

(1-2 mg/l)

AcidglutamicNH3 NH3

Urea NH4Cl

Nc tiu

M

MU

GAN THN

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TiTi gangan vv thnthn

Ti gan, NH4+ phng thch t glutamin s c tng hp thnh urea v o

thi ra nc tiu.Ti thn, thu phn glutamin cho NH4+ to mui amon v o thi theo nctiu, gip thi H+ thng bng acid-base.

Thu phn glutamin/thn tng trongtoan mu

Thu phn glutamin/thn gim trongkim mu

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Alanin vn chuyn NH4+ m c cng hot ng mnh l c v gan(chu trnh Glucose-Alanin)

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Alanine ng vai tr l acid amin quan trng trong tn to ng.

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NG DNGNG DNG

NHNH33 tng trong mu gytng trong mu gy :: Gim pH mu.Gim pH mu.

Tn thng t bo thn kinhTn thng t bo thn kinh

NHNH33 qua hng ro mu no, kt hp glutamat to glutamin gyqua hng ro mu no, kt hp glutamat to glutamin gy

gimgim keto glutarat ca no, dn ti gim oxaloacetat, nhketo glutarat ca no, dn ti gim oxaloacetat, nhhng n chu trnh Krebs, thiu nng lng cho no, tnhng n chu trnh Krebs, thiu nng lng cho no, tnthng t bo.thng t bo.

Tng glutamin trong no, gim d tr glutamat (glu cn thitTng glutamin trong no, gim d tr glutamat (glu cn thit

cho to cc neurotransmitter nhcho to cc neurotransmitter nh --aminobutyrat (GABA)aminobutyrat (GABA)))..

Tng glutamin no, thay i cht gy thm thu trong t boTng glutamin no, thay i cht gy thm thu trong t bohch glial, gy ph no.hch glial, gy ph no.

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NH3 tng trong trng hp:

- Suy t bo gan nng: x gan giai oncui, nhim c, nhim virus gy hoi t

cp..- Ni thng ca ch- Di truyn do thiu enzym ca chu trnhurea

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ChuChu trnhtrnh UreaUrea

ChuChu trnhtrnh OrnithinOrnithin

1932, Hans Krebs1932, Hans Krebs

ChCh yuyu xyxy rara gangan55 giaigiai onon (1, 2:(1, 2: xyxy rara trongtrong tyty thth

3, 4, 5:3, 4, 5: trongtrong bobo tngtng))

NN--acetylacetyl glutamatglutamat cc vaivai trtr iuiu hoho dd lplpthth dngdng..

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ChuChu trnhtrnh UreaUrea

1

23

45

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ChuChu trnhtrnh UreaUrea

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ChuChutrnhtrnhUreaUrea

CPS I: carbamylphosphat synthetaseOTC: ornithintranscarbamylase

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CHU TRNH UREA1: carbamoyl phosphatesynthetase2: ornithine transcarbamoylase

3: arginosuccinate synthetase4: arginosuccinase5: arginase

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Phng trnh tng qut:

CO2

+ NH4

+ + 3ATP + Asp + 2H2O Urea + 2ADP + 2Pi + AMP + PPi + fumarate

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RI LON CHUYN HO LIN QUAN NCHU TRNH UREA

Tng ammonia mu type 1: thiu carbamoyl phosphate synthetase

Tng ammonia mu type 2: thiu ornithine transcarbamoylase

Tng citrulline mu: thiu arginosuccinate synthetase

Tng acid arginosuccinic mu v nc tiu: thiu arginosuccinase

Tng arginine mu: thiu arginase trong hng cu

Triu chng ca cc bnh l di truyn do khim khuyt mt trong ccenzym ca chu trnh urea thng xut hin ngay sau sinh gm co git,ri lon vn ng, l m, b km, thm ch hn m hay t vong nukhng c pht hin. Nng nht l khim khuyt carbamoylphosphate synthetase.

U l d f t (UCD )

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Urea cycle defects (UCDs)

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iuiu hoho chuchu trnhtrnh UreaUrea

DiDi hnhn:: thaythay ii chch nn proteinprotein

LngLng proteinprotein caocao,, nngnng enzymenzym tngtng..

KhiKhi chch nn proteinprotein cncn bngbng,, lnglng enzymenzym gimgim..

KhiKhi ii koko didi,, tngtng phnphn huhu protein,protein, enzymenzym lili tngtng

NgnNgn hnhn: N: N--acetylglutamatacetylglutamat ll chtcht dd lplp thth dngdng cacaCPS I.CPS I.

NN--acetylglutamatacetylglutamat nn nhnh ll nhnh acetylacetyl CoACoA,, glutamatglutamat,, vvargininarginin

AcetylAcetyl CoACoA ++ glutamatglutamat NN--acetylglutamatacetylglutamat ++ CoACoA

((ArgininArginin ll chtcht dd lplp thth (+)(+) caca NN--acetylglutamatacetylglutamat synthetasesynthetase))

N-acetylglutamat synthetase

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UreaUrea--ngng dngdng lmlm sngsng

UreaUrea ll snsn phmphm thoithoi hoho chch yuyu tt protein,protein, cc totothnhthnh tt NHNH33 vv chch yuyu gangan..

KhKh nngnng toto ureaurea caca gangan rtrt lnln ((tntn thngthng 2/3,2/3, khkhnngnng toto ureaurea vnvn bnhbnh thngthng).).UreaUrea cc toto rara,, vovo mumu,, lclc thnthn vv thithi rara ncnc tiutiu..

BnhBnh thngthng::

UreaUrea mumu: 3,5: 3,5 77 mmolmmol/l/l(0,2(0,2 -- 0,4 g/l)0,4 g/l)

BUN (blood urea nitrogen)BUN (blood urea nitrogen)

TngTng hayhay gimgim ureaurea cc linlin quanquan mtmt ss tnhtnh trngtrng bnhbnh ll..

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LinLin quanquan giagia chuchu trnhtrnh UreaUrea vv chuchu trnhtrnh KrebsKrebs

Li i h t h U h t h K b

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Lin quan gia chu trnh Urea v chu trnh Krebs