emtabUlIs• 1- esckþIefþIm :famBl nigemtabUlIs : • 2- KøIkUlIs• 3- KøIkUEsnemtabUlIsnigkMNkKúøykUs• 4- vdþsuIRTikGasuIt• 5- kardwknaMeGLicRtugnigpUsVrIlkmµGuksuItkmµ• 5- kardwknaMeGLicRtugnigpUsVrIlkmµGuksuItkmµ• 6- lIBItemtabUlIs• 7- eGtaNulemtabUlIs• 8- GamINUGasuItemtabUlIs• 9- nuyekøGUTItemtabUlIs• 10- karrMlay nigkarRsUbsmasFatuGaharHeng Savoeun/2008 1

Heng Savoeun/2008 2

karsegçbkatabUlIsénGamINUGasuItÙ amino group RtUv:ndkykecj nigRtUv:nbJ©ÚleTAkñúg ureasMrabkarbeJ©jecal. eRKagqÁwgkabUnEdlenAsl´‘α-keto acid)GacRtUv:nbMEbkeTACaCO2nigH2O rWk¾bMElgeTACa glucose ,acetyl-CoArW ketone bodies

Ù GamINUGasuItEdleyIgbriePaKeTAtamcMNIGahar

Heng Savoeun/2008 3

briePaKeTAtamcMNIGaharehIyvaelIsBIesckþIRtUvkarenaH vaminRtUv:nsnSMTukeT nigvak*minRtUv:nbeJ©jecalEdr

bMElgGamINUGasuIt Õ RbtikmµcMnYn3ZM>énkarbMElgGamINUGasuIt;

1- edGamInkmµ‘Rbtikmµdkbg<úMGamIn’karbMElgbg<úMGamIneTACaGamUja¨k´ rWeTACabg<úMGamInén aspartate

2- karsg´bJ©ÚlGatUmGasUtEdlecjBIGamUj¨ak´ nig aspartate eTAkñúgurea edIm|IbeJ©jmkeRkA

3- RbtikmµbMElgGatUmkabUnénGamINUGasuItEdlRtUv:nkøayeTACaα-keto acid eGayeTAkñúglTÆplJk´kNþalTIénemtabUlIs

Heng Savoeun/2008 4

edGamInkmµ

1- edGamInkmµepÞrGamInkmµ

2- edGamInkmµGuksuItkmµ

Heng Savoeun/2008 5

1- edGamInkmµepÞrGamInkmµénGamINUGasuItÙ sMerceTAedaysarRbtikmµepÞrGamInkmµ ‘RbtikmµepÞrbg<úMGamInBIGamINUGasuIteTA

α-keto acid’Ù amino group-acceptorEdlsMxanCageK KW α-ketoglutarate

Heng Savoeun/2008 6

kUGg;suIm pyridoxal-5’-phosphate(PLP)

Ù Gg´suImEdlkatalIsRbtikmmepÞrGamInkmµ‘transamination’EdlehAzaaminotransferase rW transaminase RtUvkarkUGg´suImpyridoxal-5’- phosphate(PLP)

Ù PLP KWCaRsLay‘derivative’én pyridoxine(vitamin B6’Ù kUGg´suIm:nP¢ab´nwgGg´suIm tamry;sm¬&nÆ Schiff base(imine) Edlbeg,ItedayRbtikmµbUkén aldehyde group rbsvaCamYynwg ε-amino group rbs Lys residueRbtikmµbUkén aldehyde group rbsvaCamYynwg ε-amino group rbs Lys residue

énGg´suImÙ Schiff base KWCamCÄmNÐlskmµPaBrbskUGg´suImÙ eBl PLP TTYlyk amino group BIGamINUGasuIt enaHvakøayCapyridoxamine-5’-phosphate(PMP)

Heng Savoeun/2008 7

TMrg; pyridoxal-5’-phosphate(PLP)

c- Schiff base Edlbeg,Itrvag PLP nigε-amino group rbsGg´suIm

a-kUGg´suIm pyridoxal-

5’-phosphate(PLP)b- pyridoxine(vitamin B6’

Heng Savoeun/2008 8

dMNak;kar 1 karbMElgGamINUGasuIteTA keto acid

1- amino group rbsGamINUGasuItCa nucleophilelukluyelIGatUmkabUnénenzyme-PLP Schiff base edIm|Ibeg,It amino acid-Schiff base(aldimine)

EdlkñúgeBlCamYyKñaenaH beJ©j Lys amino group énGgsuIm2- bnÞabmk Lys enHTMenredIrtYrCa:s kñúgmCÄmNÐlskmµ2- bnÞabmk Lys enHTMenredIrtYrCa:s kñúgmCÄmNÐlskmµ3- amino acid-PLP Schiff base eZVIRbtikmµtUtUEmr‘tautomerizes’eTACaα-keto acid-PMP Schiff base(ketimine) edaykardkecjén α-H énGamINUGasuItnigRbUtugkmµénGatUm C4’rbs PLP tam resonance-stabilized

carbanion intermediate

4- α-keto acid-PMP Schiff base RtUvrgGuIRdUlIseTACa PMPnig α-keto acid

Heng Savoeun/2008 9

dMNak;kar2 karbMElg α-keto acid eTACa amino acid

Ù edIm|IbJ©b´vdþ kUGg´suImRtUvEtRtUv:nbMElgBI PMP eTACa enzyme-

PLP Schiff base vijÙ RbtikmµenH Tak´Tgnwg3CMhanRsed[gKñaxageli buEnþTisRcas

3 ´- PMP RbtikmµCamYy α-keto acid edIm|Ibeg,It Schiff base

2 ´- α-keto acid-PMP Schiff base eZVIRbtikmµtUtUEmredIm|Ibeg,Itamino acid-PLP Schiff base

1 ´- ε- amino group én Lys residue rbsmCÄmNÐlskmµlukluyelI amino acid-PLP Schiff base kñúgRbtikmµtUtUEmrkmµ edIm|Ibeg,IteLIgvijactive enzyme-PLP Schiff base nigbeJ©jGamINUGasuItEdlbeg,ItzµI

Heng Savoeun/2008 10

clnkarénRbtikmµepÞrGamInkmµ

Heng Savoeun/2008 11

2- edGamInkmµGuksuItkmµén glutamate

Ù edGamInkmµGuksuItkmµ‘oxidative deamination)én glutamate RbRBwtþeTAeRkamGMeBIén glutamate dehydrogenase rYcbeg,It:nGamUj¨ak

Ù RbtikmµenHRtUvkar NAD+ rW NADP+ CaCMnYy ehIybeg,It:n α-ketoglutarate

vijEdrvijEdr

Heng Savoeun/2008 12

vdþKøúykUs-GaLanIn (glucose-alanine-cycle)

Alanine Alanine

ezøIm Qam sac'duM

NH3 + Pyruvate Pyruvate + NH3

Glucose Glucose

Heng Savoeun/2008 13

vdþGuyer (urea cycle)Ù GamUj¨ak´BulxøaMgNascMeJHekasikaÙ PavrsTaMgGsmanpøÚvepSg> kñúgkarbeJ©jvaecalÙ stVEdlrskñúgTwk mansmtæPaBkñúgkarbeJ©jGamUj¨akedaypÞal´edaykattamekasikaénRskI

Ù BBYkstVrsenAelIeKak rMlaysMNlGasUteTACaGu)yerEdlminsUvBulÙ Gu)yerKWCalTÆplénRbtikmµEdleKehAzavdþGu)yer EdlRsaybMPøWÙ Gu)yerKWCalTÆplénRbtikmµEdleKehAzavdþGu)yer EdlRsaybMPøWedayelak Hans Krebs nig Kurt Henselett enAqñaM1932

Heng Savoeun/2008 14

smIkarRbtikmµsrubrbs;vdþGu‘yerÙ Gu)yerRtUvbeJ©jBIezøImtamQam dwknaMeTAkMrgenamEdlkñúgenaHvaRtUv:nbeJ©jmkeRkAtamTwkenam

Heng Savoeun/2008 15

Gu‘yerTamTarRbtikmµcMnYn5Ù karbJ©ÚlGamUj¨ak´ cUleTAkñúgGu)yerenHTamTarRbtikmµcMnYn5Ù Rbtikmµ cMnYn2 RbRBwtþeTAenAkñúgmItUkugRDI nigRbtikmµ cMnYn3 RbRBwtþeTAkñúgsuItUsul

1- carbamoyl phosphate synthetaseCMrujRbtikmµnigeRbI2 ATP

2- ornithine transcarbamoylase epÞrbg<úM carbamoylBI carbamoyl

phosphate eTAelI ornithine EdlkñúgenaH citrulline RtUv:nbeg,IteLIg

Heng Savoeun/2008 16

Gu‘yerTamTarRbtikmµcMnYn5

4- arginino succinate lyase CMrujRbtikmµkatpþac´arginino succinate

eGayeTACa fumaratenig arginine

3- arginino succinate synthetaseCMrujRbtikmµsgbJ©ÚlGasUtCaelIkTI2rbsGu)yer nigRtUvkar1 ATP

eGayeTACa fumaratenig arginine

5- arginase katalIsGuIRdUlIs arginine ehIybeg,It:nCaGu)yer nigornithineeLIg. bnÞab´mk ornithine RtUv:neRbIR:ssMrabvdþGu)yereRkayeT[t

Heng Savoeun/2008 17

vdþGu‘yer

Heng Savoeun/2008 18

pøÚvénkarbMElgqäwgkabUnrbs;GamINUGasuIt

Õ glucogenic bgØajBN(ébtgÕ ketogenic bgØajBN(Rkhm

Ù karrMlayRtUv:nEckCaBIrRkumKW;

Heng Savoeun/2008 19

bMElg cysteine eTACa pyruvate

ÙRtUv:nbMElgCa pyruvate ehIybg<úMsulfhydryl rbsvakøayeTACa H2S

Ù H2S RtUv:nkat´pþacBI α-C atome nigβ-C-atomeeRkam desulfhydrase

Ù eBlenaH k¾ekIt:naminoacrylate ehIyÙ eBlenaH k¾ekIt:naminoacrylate ehIybþÚrRTg´RTayeTACa iminopropionate EdlbnÞab´mkk¾køayCa pyruvate edaysarRbtikmµdkGamInkmµÙ H2S rgRbtikmµGuksuItkmµeTACa anorganicsulfate nigbeg,It:n H+

Heng Savoeun/2008 20

karbMElg serine eTACa pyruvate

Ù clnkarrbs serine dehydrogenase~gkarbMElg serineÙ Gg´suImEdlGaRs&yPLPkatalIskarbM:tTwkBI serinekñúg6CMhan

1- karbeg,It serine-PLP Schiff base2- kardk α-H atom én serine edIm|Ibeg,It resonance-

stabilized carbanion

3- karbM:t3- karbM:t β-OH

4- GuIRdUlIsén Schiff base edIm|Ibeg,It PLP-enzyme nig aminoacrylate

5- tUtUEmrkmµedayKµanGg´suImeTACa imine

6- GuIRdUlIsedayKµanGg´suImedIm|Ibeg,It pyruvatenigammonia

Heng Savoeun/2008 21

karbMElg serine eTACa pyruvate

Heng Savoeun/2008 22

RbtikmµbMElg alanine, serine nig threonine eTACa pyruvate

Ù alanine rgRbtikmµepÞrbg<úMGamIneRkamGMeBIén alanine amino

transferase køayeTAkøayeTACa pyruvate

Heng Savoeun/2008 23

bMElg asparagine nig aspartate eTACaoxaloacetate

Ù asparagine RtUvrgRbtikmµGuIRdUlIseRkamGMeBIén asparaginase køayeTACa aspartate

Asparagine + H2O → Aspartate + NH4+

Ù aspartate rgRbtikmµepÞrbg<úMGamIn‘transamination)edaypÞal´ ehIykøayeTACaoxaloacetate nigkatalIseday aminotransferase

Aspartate + α-Ketoglutarate → Oxaloacetate + Glutamate

Heng Savoeun/2008 24

bMElg phenylalanine nig tyrosine eTACafumarate nig acetoacetate

Ù karrMlay phenylalanine KWCaRbtikmµGuIRduksuIlkmµedIm|IeGay køayCa tyrosineeday phenylalanine hydroxylase

ÙbnÞab´mk GamINUGasuItTaMgBIrenHRtUvbMElgelIpøÚvEtmYyEdlman 6CMhan rhUtdlkøayCa fumarate nig acetoacetate

Ù tyrosine:tbg´ amino-group rbsxøÜntamry;RbtikmµepÞr Ù tyrosine:tbg´ amino-group rbsxøÜntamry;RbtikmµepÞr GamIneTACa α-ketoglutarateEdlCMrujeday tyrosine

transaminase

Ù 4-hydroxyphenylpyruvate eRkamGMeBIén 4-hydroxyphe-nylpyruvate hydroxylasekøayCa homogentisate

Heng Savoeun/2008 25

Ù CMhanbnÞab´eT[t KWrgVg´ banzolRtUv:nkat´pþacedaykarbJ©Úl mUelKul O2 edayhomogentisate dioxygenase

Ù 4-maleylacetoacetate køayCa fumarylacetoacetate

Ù fumarylacetoacetate

k¾køayCa fumarate nig k¾køayCa fumarate nig acetoacetateedayGuIRdUlIs

Heng Savoeun/2008 26

sar³sMxan;én phenylalanine hydroxylase

Ù cMeBaHGñkCMgW EdlGvtþmanén phenylalanine hydroxylase

bNþaleGay phenylalanine kkKr~gQam

Ù phenylketonuria CaCMgWemtabUlIsBIkMeNItEdlbNþalmkBIGvtþmanén phenylalanine hydroxylase enA~gezøIm

bNþaleGay phenylalanine kkKr~gQam

Ù karkkKrén phenylalanine ~gCalika KWBulcMeBaHkarvivDÄn¾énCalikaxYrk|al dUcCa xUcxYrk|al‘brain damage) nigkaryWty¨avxagR:C\a‘progressive mentalretardation)

Heng Savoeun/2008 27

GamINUGasuItsMrab;karsMeyaKmU:elKulepSg

Ù GamINUGasuItmYycMnYn KWCaCMhanTImYyénkarsMeyaKmUelKulEdlcaM:c´bMput dUcCa

- nuyekøGUTIt ‘nucleotid)- nuyekøGUTIt-kUGg´suIm ‘nucleotid-coenzyme)

EGm ‘- EGm ‘heme)

- GrmUn ‘hormone)

- GñkbJ¢ÚnsarRbsaT ‘neurotransmitter)

- Køúytasüúg ‘glutathion)

Heng Savoeun/2008 28

EGm (heme)

Ù EGmKWCa prosthetic groupénRbUetGuInCaeRcInEdlmanCatiEdk‘Fe’ó hemoglobine,

myoglobine nig cytochromenig

Ù enAqñaM1945 elak David Shemin nigElak David Rittenberg:nbgØajza;GatUmkabUn nigGatUmGasUtTaMgGs´kñúgEGmmkBI succinyl-CoA nig glycine

Heng Savoeun/2008 29

EGm (heme)

Heng Savoeun/2008 30

GaeRTNalIn (adrenalin) nGaeRTNalIn (noradrenalin) nigdU)a:mIn (dopamine)

Ù GaeRTNalIn nignGaeRTNalIn KWCaGrmUnEdlelIkkMlaMg‘stimulation’eGaymankarrMlayKøIkUEsnedIm|IrkSakMhab´KøúykUskñúgQam

Ù karsMeyaKGaeRTNalIn nignGaeRTNalIn KWCaedkabuksuIlkmµ‘decarboxylation’én tyrosine

Heng Savoeun/2008 31

karbMElg tyrosine

Ù karbMElg tyrosine RbRBwtþeTAdUcteTA ;- tyrosine rgGuIRdUlIseRkamGMeBIrbs tyrosine hydroxylase

ehIyvaRtUvbMElgeTACa 3, 4-dihydroxyphenylalanine (DOPA)

DOPA RtUvrgRbtikmµedkabuksuIlkmµeTACa dU:¨mIn EdlCaGñkbJ¢ÚnsarRbsaT‘neurotransmitter)enAkñúgsuINab‘synapse) énxYrk|al

Heng Savoeun/2008 32

RbtikmµsMeyaK adrenalin,

noradrenalin nigdopamine

dU:¨mIn rgRbtikmµGuIRdUlIseTACa- dU:¨mIn rgRbtikmµGuIRdUlIseTACanGaeRTNalIn- nGaeRTNalIn RtUvbMElgeTACaGaeRTNalIneRkamGMeBIénphenylethanolamin N-

methyltransferase

Heng Savoeun/2008 33

Køúytasüúg (glutathion, GHS)

Ù KWCaRTIbuibTIt‘tripeptide)EdlekIteLIgBI glutamate, cysteine nig glycine

nigCMrujeday glutamyl cystein synthetase nig GSH-synthetase

Ù Køúytasüúg mannaTICaGñkbM:tCatiBulkñúgxøÜneyIg‘CaGñkrMlayEBGuksuIt‘peroxide) EdlRtUv:nsMeyaKeday oxidase’

R2O2 2ROH NADPH NADP+

2GSH GSSG 2GSH

Glutathion peroxidase Glutathion reductase

Heng Savoeun/2008 34

karsMeyaKGamINUGasuIt Ù GamINUGasuItCaeRcInRtUv:nsMeyaKedayruk¡Cati nigmIRkUsarBag<kayÙ mnusS GacsMeyaK:nEtGamINUGasuItmYycMnYnbueNÑaH kñúgcMeNam

GamINUGasuItEdlxøÜneyIgRtUvkar

non essential amino acid essential amino acid

glycine

serine

threonine

valineserine

cysteine

alanine

aspartate

asparagine

glutamate

glutamine

proline

tyrosine

valine

histidine

arginine

methionine

leucine

lysine

isoleucine

phenylalanine

tryptophan

Heng Savoeun/2008 35

karsMeyaKGamINUGasuIt

Heng Savoeun/2008 36

karsMeyaKGamINUGasuItminsarvnþ

ÙRKb´GamINUGasuItminsarvnþTaMgGsRtUv:nsMeyaKeLIgtampøÚvd*gayEdlecjBIZatuepþImcMnYn4 KW

- pyruvate

- oxaloacetate

- α-ketoglutarate

- 3-phosphoglycerate

edayRKanEteZVIRbtikmµepÞrbg<úMGamInkmµ

Heng Savoeun/2008 37

karsMeyaK alanine

Ù Alanine RtUvbMElgtamry;RbtikmµepÞrGamInkmµeTAelI pyruvate EdlkatalIseday aminotransferase

Heng Savoeun/2008 38

karsMeyaK aspartate

Ù aspartate RtUv:nsMeyaKecjBI oxaloacetate tamry;RbtikmµepÞrGamInkmµEdlkatalIsedayGgsuIm aminotransferase

Heng Savoeun/2008 39

karsMeyaK asparagine

Ù asparagine ekIteLIgBI aspartate eRkamGIeBIénGg´suIm asparagine

synthetase EdleBlenaH glutamine CaGñkpþl´ amino-group

Heng Savoeun/2008 40

karsMeyaK glutamate

Ù glutamate RtUv:nsMeyaKBI α-ketoglutarate eRkam«TÆiBlrbs aminotransferase

Heng Savoeun/2008 41

karsMeyaK glutamine

Ù glutamine ekIteLIgBI glutamate edaysar glutamine synthetase

Ù Gg´suImenHmaneRcInenA~gsac´duM sYt xYrk|al ezøIm kMrgenamnigCalikaxøaj´

Ù glutamine ~g:øsµamanmuxgarsMxanNassMrab´dwknaMeRKagkabUn nigGasUtrvagsrIrag< nigsrIrag< CaBiess KWBIxYrk|al nigsacduM eTAkMrgenam ezøIm

Heng Savoeun/2008 42

karsMeyaKproline

Ù glutamate KWCamUelKuledImsMrab´ykeTAsMeyaK proline

Ù prolineCaZatuepþImén hydro-

xyproline EdlCaGamINUGasuItmYyd¾sMxan~gkarsMeyaK

Heng Savoeun/2008 43

mYyd¾sMxan~gkarsMeyaKcollagen(10-15%) nigelastine(1-3%)

Ù ~gcollagenman prolinenighydroxyprolinerYmKña RbEhl25% énGamINUGasuItTaMgGs

karsMeyaK serine

serine RtUv:nbeg,IteLIgBI 3-phosphoglyceratekñúgRbtikmµ cMnYn3bnþbnÞab´KñaKW;

k’ bMElg 2-OH-group rbs 3-phosphoglycerate

eGayeTACa 3-phosphohydroxypyruvatex’ RbtikmµepÞrbg<úMGamInén 3-phospho-x’ RbtikmµepÞrbg<úMGamInén 3-phospho-

hydroxypyruvateeTACaphosphoserineK’ RbtikmµGuIRdUlIsén phosphoserine eTACa serine

Heng Savoeun/2008 44

karsMeyaK glycine

glycineRtUv:nsMeyaKecjBI serineedaypÞaleRkamGMeBIén hydroxymethyl

transferasetransferase

Heng Savoeun/2008 45

karcab;ykGasUt

Ù GasUtsæitkñúgTMrg´Caósµ&n‘N2’EdlmanRbEhl80PaKryénbriyakasÙ GatUmTaMgBIrénmUelKulGasUtcgP¢ab´Kñaedaysm¬&nÆbICany¨agCab´Ù KuNPaBEbbenHeZVIeGayósµ&nGasUttamlk¡N;KImIKµanlTÆPaBeZVIRbtikmµKImIeT

Ù dUcenH edIm|ICMrujeGayvaeZVIRbtikmµKImIRtUvTamTarCacaMlTÆPaBeZVIRbtikmµKImIeT

Ù dUcenH edIm|ICMrujeGayvaeZVIRbtikmµKImIRtUvTamTarCacaM:c´nUvGg´suImy¨agBiessNas( complex enzyme nitrogenase)

Heng Savoeun/2008 46

rwsénBBYksENþkÙ Gg´suIm nitrogenase manenAkñúgBBYk:k´etrIrhizobium EdlrsenACalk¡N;shR:N‘symbiose)kñúgzñaMgénrwsrbsruk¡Cati leguminose dUcCasENþkRKab´mUl sENþk :raMgalfalfa nig clover‘eRK}geTs’

BYk:k´etrIrsenAnwgzñaMgénrwsEdlCaGñkcab´ykGasUtBIbridðan nigbMElgeTACa NH3

Heng Savoeun/2008 47

vdþGasUt (nitrogen cycle)

Ù BBYk:k´etrIrsenAelIdI nigBBYkmIRkUsarBag<kayrsenACalk¡N;shR:N GacbMElgGasUt‘N2’eTACaGamUj¨ak´. GamUj¨ak´enHRtUvykeTAsg´bJ©ÚlkñúgmUelKulCIv;dUcCa RbUetGuInÙ BYk:k´etrIPaKeRcIn nigruk¡CatiGnuvtþRbtikmµerdukmµénnIRtateTACaGamUj¨ak´tamnIRTItÙ :k´etrIxøHGacbMElgGamUj¨ak´eTACanIRTIt. xøHGaceZVIGuksuItkmµnIRTIt eTACanIRtat ehIyxøHeT[tGaceZVIRbtikmµerdukmµnIRtateTACaGasUt

Heng Savoeun/2008 48

glutamate dehydrogenase CMrujRbtikmµbBa©Úl GamU:j:ak;eTAkñúg glutamate

Ù karsg´bJ©ÚlénGamUj¨ak´ eTAelI α-ketoglutaratebeg,It:n glutamate

Ù RbtikmµenHRtUvCMrujedayGg´suImmYykñúgruk¡Cati eQµaHza glutamate

dehydrogenase

Heng Savoeun/2008 49