7. amino acid metabolism [compatibility mode]
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Transcript of 7. amino acid metabolism [compatibility mode]
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