2. citric acid cycle

emtabUlIs• 1- esckþIefþIm :famBl nigemtabUlIs : • 2- KøIkUlIs• 3- KøIkUEsnemtabUlIsnigkMNkKúøykUs• 4- vdþsuIRTikGasuIt• 5- kardwknaMeGLicRtugnigpUsVrIlkmµGuksuItkmµ• 6- lIBItemtabUlIs• 6- lIBItemtabUlIs• 7- eGtaNulemtabUlIs• 8- GamINUGasuItemtabUlIs• 9- nuyekøGUTItemtabUlIs• 10- karrMlay nigkarRsUbsmasFatuGahar

Heng Savoeun/2008 1

Citric Acid CycleCitric Acid Cycle

Heng Savoeun/2008 2

Ù eBlEdlGatUmkabUnén«nÞn;emtabUlIs R tUvrgGuksuItkmµeTACa‘

Ù TTYlra¨brgR bti kmµGuksuItkmµ kabUGuIR dat GasuItxøaj´ ni gGamINUGasuItni gplitnUvsarZatuedImCaeRcInsMrab´sMey aKCIv;

vdþGasuItsuIRTic rW vdþ krebs

Ù eBlEdlGatUmkabUnén«nÞn;emtabUlIs R tUvrgGuksuItkmµeTACaCO2 enaHeGLi cR tugRtUv: nepÞreTAeGay GñkyYreGLicRtug ‘electroncarrier’ ehIy EdlbnþbnÞab´mkrgGuksuItkmµeday GuksuIEsn

Õ elak Hans Aldolf Krebs : ncabépþImeZVIkarR savR CavGMBIkarbMEbksu) bR sþaenA~gTsSvtSTI30 ehIy : nbJ©b´bnÞab´BIsR g<amelakelIkTI2

Heng Savoeun/2008 3

«nÞn;GuksuItkmµemtabU lIs (oxidative fuel metabolism)

acetyl groupmk BI k abUGuIRdat GamINUGasuIt GamINUGasuIt GasuItx ø aj´

cUl eT Akñ úg citric acid cycleCak Enø g Edl v aRtUv rgGuk suItk mµ eT ACa CO2

Heng Savoeun/2008 4

karsMeyaK acetyl-CoenzymeA

Ù acetyl-CoARtUv:nbe g,ItBI pyruvateta mry; oxidative decarboxylation e daymultienzyme complex E dlmane QµaHza pyruvate dehydrogenase

Ù kMue bø ce nHmanGg´suIm3 ; pyruvate dehydrogenase(E1), dihydrolipoyl

transacetylase(E2) nig dihydrolipoyl dehydrogenase(E3)

Heng Savoeun/2008 5

RbtikmµTaMg5rbs; pyruvate dehydrogenase multienzyme complex

Ù E1(pyruvate dehydrogenase) man TPP nigkatalIsRbtikmµ1nig2Ù E2 (dihydrolipoyl transacetylase) man lipoamidenigkatalIsRbtikmµ3Ù E3(dihydrolipoyl dehydrogenase) E dlman FAD nig redox-active

disulfide e hIykatalIsRbtikmµ4 nig5

Heng Savoeun/2008 6

dMeNIrénvdþGasuItsuIRTic

Heng Savoeun/2008 7

RbtikmµénvdþGasuItsuIRTic

1’ citrate synthase CMrujRbtikmµbUkrvag acetyl-coA nigoxaloacetate e hIybe g,It:nCa citrate

Õ Rkum CH3 én acetyl-CoA RtUv:nbUkbJ ©Úle TAe lIRkum C=O e nAnwgoxaloacetate e hIysm¬&nÆ thioester k¾RtU:npþacé hIysm¬&nÆ k¾RtU:npþac´

Heng Savoeun/2008 8

clnkarRbtikmµ: nesñIeday James Remington KWR cvakćM eh[g3EdlGackøay CaGuIyu grbs ´ citrate synthase cUlrYmkñúgkatalIs;k- enol én acetyl-CoARtUv:nbe g,Ite LIg e Bl Asp375‘:s’ dkykRbUtug

e cjBI methyl group e hIynig His 274‘GasuIt’ e ZVIRbUtugkmµ enolate

oxygenoxygen

x- citryl-CoA RtUv:nbe g,ItkñúgCMhanTI2 E dlkñúge naH acetyl-CoA enol

(nucleophile) lukluy oxaloacetate. His 274dkykRbUtugE dl:ne GayBImun nig His 320 ‘GasuIt’ pþl´RbUtuge TAe Gaycarbonyl group én oxaloacetate

Õ citryl-CoA-intermediate e nAE tcg´sm¬&nÆ CamYyGgsuImK- citryl-CoA rgGuIRdUlIse TACa citrate nig CoA

Heng Savoeun/2008 9

clnkarRbtikmµ

Heng Savoeun/2008 10


2’ aconitase bMElg citrate eTACa isocitrate nigpþac Twkec jÙ aconitase katalIsRb tikmµGuIsUEmrkmµe T Amk rb scitrate nig isocitrate



3’ isocitrate dehydrogenaseCM rujRb ti kmµGuksuItk mµ isocitrate

ehIyb eg,It:n NADH, α-ketoglutarate nigb eJ©j CO2ec alÕ enHKWCMhandMbUgEdlb eJ© j CO2

Õ NAD+ RtUvrgerdukmµeTA CaNADHÕ RtUvrgerdukmµeTA Ca


RbtikmµénvdþGasuItsuIRTic4’ α-ketoglutarate dehydrogenase complex CMrujRb tikmµ

GuksuItkmµdkkabUnec jBI α-ketoglutarateÕ Rbtikmµe nHbe J ©j:n1mU e lKul NADH nig CO2

Õ CO2 RtUv:nbe J ©je calCae lIkTI2 mann&yza GuksuItkmµrbsbg<úMGae sTIl RtUv :nbJ ©b´Gae sTIl RtUv :nbJ ©b´


RbtikmµénvdþGasuItsuIRTic5’ succinyl-CoA synthetasebMElg succinyl-Co AeTACa succinateÕ zamBlE dlmane nAkñúgsm¬&nÆ thioester én succinyl-CoA RtUv:n

pÞúke daysarkarsMe yaKmU e lKul GTP e cjBI GDP

ÕRbtikmµE dlbe g,ItGTP re b[be nH e hAza substrate level-phosphorylation


clnkar3CMhanrbs;clnkar3CMhanrbs;clnkar3CMhanrbs;clnkar3CMhanrbs; succinyl-CoA synthetase

k - succinyl-CoA eZVIRbtik mµCamYy Pi edIm|Ibeg,It succinyl-phosphate nig CoA

x - bnÞ ab´mk phosphoryl

group RtUv :nep Þ rBI group RtUv :nep Þ rBI succinyl-phosphate eT A eGay His residue rbsGg´suImedaybeJ©j succinate

K- phosphoryl group

enAel IGg´suIm RtUv :nep Þ reGay GDPedaybeg,ItGTP



6’ succinate dehydrogenase complex CMrujRb tikmµbMElgsuccinate eTACa fumarate

Õ G gsuImenHCMrujRb tik mµkñúg karb e g,Itsm¬& nÆ BI rC an´Õ FADH2 RtUv:nb eg,IteLIgBI FAD


RbtikmµénvdþGasuItsuIRTic7’ fumarase CMrujRb tikmµGuIRdatkmµRtLb ´‘reversible hydration)

én fumarate eTACa malate

Õ fumaraseCMrujsmIkartulü P aBénka rbMEl gfumarateeTACamalate edaykarbUkTwke T AelIs m¬&nÆ BIr Can´ rb s´ fumarate


RbtikmµénvdþGasuItsuIRTic8’ malate dehydrogenase CMrujRb tikmµGuksuItkmµén malate

eTACa oxaloacetate

Õ CMh)ancuge Rkaye nAkñúgvdþGasuItsuIRTicKWCaRbtikmµGuksuItkmµé n malate

e dIm|Ibe g,It:nmkvijnUv oxaloacetate E dlkñúgRbtikmµe naHbe g,It:n1 NADH:n1 NADH


famBlénvdþGasuItsuIRTicÕ s mIkars rub

Acetyl-CoA + 3NAD+ + FAD + GDP + Pi → CoA + 3NADH

+ FADH2

+ GTP + 2CO2


NADH nig FADH2 plit ATP

tamRbtikmµpUsVrIlkmµGuksuItkmµ

Ù 1NADHbeg,It: n 3ATPKWenAeBlEdl NADH R tUvrgR bti kmµGuksuItkmµeTACa NAD+ eday R cvak´dwknaMeGLicRtug

Ù 1 beg,It:n2 KWenAeBlEdl R tUvrgR bti kmµÙ 1FADH2 beg,It:n2 ATP KWenAeBlEdl FADH2 R tUvrgR bti kmµGuksuItkmµeTACa FAD eday R cvak´dwknaM eGLicR tug


famBlsrub


karEktMrUvvdþGasuItsuIRTic

1’- karEktMrUveTA elIsk mµP aB pyruvate dehydrogenase complex

CaTUeTA su)b Rsþa(pyruvate), NAD+ nig coenzymeA KWCaGñ keZVIeG ayskmµénG gsuImenH nigacetyl-CoA nig NADH KWGñ kb gÁak‘inhibitor’

2’- citrate synthase RtUv:nb gÁakeday ATP2’- RtUv:nb gÁakeday

3’- isocitrate dehydrogenase RtUv:neZVIeG ayskmµeday ADP ehIyRtUveZVIeG ayG skmµeday ATP nig NADH tamlk¡N; allosteric

4’- succinate dehydrogenase RtUv:nb gÁakéday oxaloacetate tamlk¡N;feedback-inhibition


karEktMrUvvdþGasuItsuIRTic

Citrate

synthase

ATP

succinate

dehydrogenase

synthase


RbtikmµxøHEdlpþl;GnþrsmasFatu cUlkñúgvdþsuIRTicGasuIt

ÙdüaRkame nHbgØ aj TItaMgE dle nA Rtgé naH GnþrsmasZatuRtUv:n KUsc|assMrab´kare RbI

Ù RbtikmµE dlTakTgnig Ù RbtikmµE dlTakTgnig e pÞ rGamInkmµ nige dGamInkmµénGamINUGasuIt KWRTLbé TAmk


vdþKøIGuksuILatÕ ruk¡Cati‘minE mnstV’manGg´suImE dlmansmtæ PaBkñúgkarbMElg acetyl-

CoA e Gaye TACa oxaloacetate E dlGacRtUv:ne RbIsMrabkMN kKøúykUsÕ karbME lge nHRbRBwtþe TAe RkamGMe BIénGg´suImrbsvdþKøIGuksuILat

‘glyoxylate-cycle)E dlmankarcUlrYmBIGg´suIménmItUkugRDI nigKøIGuksuIsUm‘glyoxysome)E dlCaZatue kasikaruk¡CatimanPñ asruMCit‘glyoxysome)E dlCaZatue kasikaruk¡CatimanPñ asruMCit

ÙsmIkarsrub KWkarb eg,It:n oxaloacetate BI 2 acetyl-CoA:

2Acetyl-CoA + 2NAD+ + FAD → Oxaloacetate +

2CoA + 2NADH +

FADH2 + 2H+


vdþKøIGuksuILat kñúgrukçCati

G gsuIm isocitrate-lyase

nig malate-synthaseKWCaG gsuImEdl ma nenAE tkñú gruk¡Catiruk¡Cati


Food

2. citric acid cycle