8. nucleic acid metabolism [compatibility mode]

emtabUlIsemtabUlIs• 1- esckþIefþIm :famBl nigemtabUlIs : • 2- KøIkUlIs• 3- KøIkUEsnemtabUlIsnigkMNkKúøykUs• 4- vdþsuIRTikGasuIt• 5- kardwknaMeGLicRtugnigpUsVrIlkmµGuksuItkmµ• 5- kardwknaMeGLicRtugnigpUsVrIlkmµGuksuItkmµ• 6- lIBItemtabUlIs• 7- eGtaNulemtabUlIs• 8- GamINUGasuItemtabUlIs• 9- nuyekøGUTItemtabUlIs• 10- karrMlay nigkarRsUbsmasFatuGahar• 11- rsµIsMeyaK

Heng Savoeun/2009 1

Nucleic Acid MetabolismNucleic Acid Metabolism

Heng Savoeun/2009 2

TMrg;KImIrbs;nuyekøGUTItÙ nuy e kø GUTIt‘nucleotide)KWCapUsVate GE sÞ ‘phosphatester) r b s

s,r b g ´tUs‘s,r C5’ E d lkñ úg e naH: sGasUtcg sm¬&nÆ CamYy C-1 éns,r b ¨ g tUsÙ : sGasUt

Heng Savoeun/2009 3

I- karsMeyaKénnuyekøGUTIt

1- rIb Un uye kø GUTIt ‘ribonucleotide)1- 1 Buy r In- r IbUnuy e kø GUTIt‘purine-ribonucleotide)1- 2 BIr ImIDIn- r IbUnuy e kø GUTIt‘pyrimidine-ribonucleotide)

2- e d GuksuIrIb Un uye kø GUTIt ‘deoxyribonucleotide)2- 1 kar b e g,It e d GuksuIr IbUs‘deoxyribose)2- 2 kar b e g,It Thymine

Heng Savoeun/2009 4

1- rIbUn uye kø GUTIt ‘ribonucleotide)

Heng Savoeun/2009 5

1-1 BuyrIn-rIbUnuyekøGUTIt‘(purine-ribonucleotide)Ù qñ aM194 8 e lak John Buchanan : ne ZVIBie saZn*e d ay e Gay

cMN IstVRJ b E d lm ansar Zatu isotope markerepSg >Kñ a r YcKate ZVIkar v iPaKe TAe lITItaMg énGatUm E d lkMN tsMKale naH‘marker’ e nAkñ úg GasuItGu)y r ic‘uric acid) E d lstVRBab e naHb e J ©jm ke RkA

Heng Savoeun/2009 6

karBiesaFn¾bgðaj

- N(1) é n Buyr In m k BIb g<úMGamIn r b s aspartate

- C(2) nig C(8) é n Buyr In m k BI formyltetrahydrofolate- N(3) nig N(9) é n Buyr In m k BIb g<úMGamIn r b s glutamine

- C(4), C(5) nig N(7) é n Buyr In m k BI glycine- C(6) é n Buyr In m k BI CO2

Heng Savoeun/2009 7

karsMeyaK IMP

Ùcab ´ep þIm mun dMb Ug KWk ar sMeyaK inosine 5-monophosphate(IMP)

Ù inosine 5-monophosphateRtUv : n sMe yaK e LI gt am p ø Úv mYy Edl m an Rb tik mµcMnYn 11KW;1’ k ar eZVIeGaysk mµé n ribose 5-phosphate

sar ZatuedIm sMr ab ´ sM eyaK Buy r In KW D-ribose 5-phosphate Edl Cap l it p l m k BIdMeN Ir p UsVat b ¨ g´tUs

Heng Savoeun/2009 8

2 ’ k ar sg´b J ©Úl N(9)é n Buyr In Edl CMr ujeda y amidophosphoribosyl transferase

3’ k ar sg´b J ©Úl C(4), C(5) nig N(7)Edl RtUv k ar 1 ATP

4 ’ k ar sg´b J ¢ Úl C(8)Edl RtUv : n CMr ujedayG g´ suIm glycine amid ribotid transformylase

5 ’ k ar s g´b J ©Úl N(3)e day sar Gg´ suIm formylglycine amid ribotid synthetase nigRtUvkar1ATP

6’ k ar b eg,It purine-imidazol Edl CMr uj e day Gg´ suIm amino imidazolribotid synthetase

nigRtUv k ar 1 ATP

7’ k ar sg´b J ©Úl C(6) Edl amino imidazolribotid carboxylase

8’ k ar sgb J ©Úl N(1) Edl CMr ujeday 5- amino imidazol 4-ribotid synthetase nig8’ k ar sgb J ©Úl N(1) Edl CMr ujeday 5- amino imidazol 4-ribotid synthetase nigRtUv k ar 1 ATP

Heng Savoeun/2009 9

9’ k ar dk fumarateeday adenyl succinate lyase

10 ’ k ar sg´b J ©ÚlC(2)eday 5- amino imidazol 4-carboxyamidribotid transformylase

11’ k ar b eg,It IMPedayk ar k at ´p þacT wk

Heng Savoeun/2009 10

karsMeyaK adenine-

nig guanine-

ribonucleotide

ecjBI IMP


karsMeyaK nucleosiddiphosphate(NDP) nignucleosidtriphosphate(NTP)

Ù NDP nig NTP RtUv : n sMeyaKecjBI nucleosid-monophosphate(NMP)t amr y; Rb tik mµp UsVr Il k mµ

AMP + ATP Nucleosidmonophosphate kinase 2ADP

GMP + ATP Nucleosidmonophosphate kinase GDP + ADP

GDP + ATP Nucleosid-diphosphate kinase GTP + ADP


1-2 karsMeyaKBIrImIDIn-rIbUnuyekøGUTIt(pyrimidine ribonucleotide)


1-2 karsMeyaKBIrImIDIn-rIbUnuyekøGUTIt(pyrimidine ribonucleotide)

Ù t am k ar BiesaZn*edayeRb I isotope : n b gØ ajza;- N(1), C(4), C(5) nig C(6) é n BIr ImIDIn m k BI aspartate- C(2) é n BIr ImIDIn m k BI HCO3

-

- N(3) é n BIr ImIDIn m k BI glutamine


karsMeyaK uridine monophosphate (UMP)

Ù kñ úg kar sMe y aK UMP m anRb tikmµcMnYn6 d Ucte TA;1’ kar sMe y aK carbamoylphosphateecjBI HCO3

- nig amid

r b sglutamineE d lCMr uje d ay carbamoyl-phosphate

synthetase II nig RtUv kar 2 ATP

2’ kar sMe y aK carbamoyl aspartate RtUv : nCMr uje d ay2’ kar sMe y aK RtUv : nCMr uje d ayaspartate transcarbamoylase

3 ’ kar b e g,It dihydroorotate RtUv : nCMr uje d ay dihydroorotase

4 ’ Rb tikmµGuksuItkmµén dihydroorotate e Rkam GMe BI dihydroorotatedehydrogenase


5 ’ kab e g,It orotidin 5-mono-

phosphateE d lkatalIse d ayorotate phosphoribosyl

transferase

6 ’ e d kabuksuIlkmµ KWCaRb tikmµe d kabuksuIlkmµ orotidin5-monophosphate e Gay e TA

Ca e Rkam GMe BIénGgsuIme Gay e TA

Ca UMP e Rkam GMe BIénGgsuImorotidin monophosphate

decarboxylase


karsMeyaK UTP

Ù R bR Bwtþe TACaBIr dM Nak ´k ar EdlRtUv :nCMruj eday nucleosid

monophosphate kinase ni g nucleosid diphosphate kinase

UMP + ATP UDP + ADP

UDP + ATP UTP + ADP


karsMeyaK cytidinetriphosphate (CTP)

Ù CTP-synthase s M e y aK CTP BI UTP e day e ZVIk ar bþÚr bg <úM GamIn

glutamine glutamate

CTP synthetase

H2O + ATP Pi + ADP


I- karsMeyaKénnuyekøGUTIt

1- rIb Un uye kø GUTIt ‘ribonucleotide)1- 1 Buy r In- r IbUnuy e kø GUTIt‘purine-ribonucleotide)1- 2 BIr ImIDIn- r IbUnuy e kø GUTIt‘pyrimidine-ribonucleotide)1- 2 BIr ImIDIn- r IbUnuy e kø GUTIt‘

2- e d GuksuIrIb Un uye kø GUTIt ‘deoxyribonucleotide)2- 1 kar b e g,It e d GuksuIr IbUs‘deoxyribose)2- 2 kar b e g,It Thymine


2- e d GuksuIrIbUn uye kø GUTIt ‘deoxyribonucleotide)


Ù deoxyribonucleic acid (DNA) xusBI ribonucleic acid (RNA)Rtg BIr cMN uc KW DNA m ans,r 2-deoxyribose nig m an: s

CMnYs

2-1- karbegáItedGuksuIrIbUs ‘deoxyribose)

Rtg BIr cMN uc KW m ans,r nig m an: sthymine CMnYs uracil

Ù deoxyribonucleotide RtUv : nb e g,Ite LIg BI ribonucleotide e d aysar Rb tikmµe r d ukmµén C(2)


2-1- karbegáItedGuksuIrIbUs (deoxyribose)Ù Gg´suIm Edl CMr ujRb tik mµer duk mµé n ribonucleotideedIm |Ib e g,It deoxyribonucleotide en H KW

ribonucleotide reductase


ribonucleotide reductase

Ù r Ub b b gØ ajBI β subunit BIr duMEdl b gØ ajBN ( el ] g nigex [v .Fe(III) ion tMN agedayBN (T wk Rk Uc.

Ù r Ub c b gØ aj binuclear Fe(III) complex . Fe(III) ion nimYy> RtUv : n tMEr tMr g´edayHis N atom nig 5 O atom Edl r Ym T aMg O2- ion r b sv a nigGlu carboxyl groupEdl P¢ ab ´s¬an 2 Fe(III) ion.Heng Savoeun/2009 23

2-2 karsMeyaKthymine

dTMP é n DNA RtUv: n sMeyaKeLIg edaysar Rb tik mµb Uk b g<úMmethyl é n dUMPmethyl é n dUMP

eRk am GMeBIr b s G g´ suImthymidylate synthase


II- karbMEbknuyekøGUTIt

ÙGasuIt nuyek ø Guicmin RtUv : n b MEb k edaysar Ga suIt é n Rk BHeT Biessv a RtUv : n b MEb k en Ak ñ úgduodenumeRk am GMeBInucleaseé n l MEBgnigintestinate phosphodiesterase

eT ACanuyek ø GUT It r b sv aÙ nuyek ø GUT It en Hmin Gacqø gk at ´Pñ as ek asik a: n eT dUcen Hv aRtUv r gnUv GuIRdUl Iseday sarspecific nucleotidasenig non specific phosphatase eT ACanuyek ø GUsuItspecific nucleotidasenig non specific phosphatase eT ACanuyek ø GUsuItÙ nuyek ø GUsuIt GacRtUv : n RsUb yk eday eJ H ev [n r WRtUv : n b MEl geRk am GMeBInucleosidase nig nucleosid phosphorylase eT ACa: snigr Ib Us r W ribose 1-phosphate

Nucleosid + H2ONucleosidase Base + Ribose

Nucleosid + Pi Nucleosid phosphorylase Base + Ribose 1-P


1-karbMElgBuyrIn

Ù purine nucleotide nig purine deoxynucleotid RtUv : nbME lg r hUtd l´GasuItGu)y r ic‘uric acid)

Ù - adenosine nucleosid RtUv : nbME lg e d ay GMe BIénGg suImadenosine deaminase

- adenosine nucleotide RtUv : nbME lg e d ay GMe BIénGg suIm- adenosine nucleotide RtUv : nbME lg e d ay GMe BIénGg suImAMP-deaminase


pø Úv énkar bME lg AMP nige TACaGasuItGu)y r ic

pø Úv énkar bME lg nigGMP e TACaGasuItGu)y r ic‘uric acid)


karxVH adenosine deaminase bNþaleGaysøab;

Ù k ar r Gak ´r GYl é n Esn Edl Gac eZVI e Gay sk mµPa Br b s adenosine

deaminase : t ´b g´ k *b N þal eGayem t ab Ul Isé n purine nucleotidmin dMeN Ir k ar Edl Caehtue ZVI eGa yLaMp U suIt ‘lymphocyten): t ´b g´

k ¾b N þal eGayek It CMgW servere cambined immunodeficiencydisease (SCID) Edl sø ab T aMgen Av &yek µg

Ù LaMp UsuIt KWCaRb ePT mYyé n ek asik as r b sRk um agranulocyte Edl RtUvEdl sø ab T aMgen Av &yek µg

Ù LaMp UsuIt KWCaRb ePT mYyé n ek asik as r b sRk um agranulocyte Edl RtUv: n b eg,It eLIgen Ak ñ úgx Yr qÁw g ehIyv ak *v iv D¿eT ACaek asik aBIr ep S g Kñ a KWmYyeQµaHza B-Cell nigmYyeT [t eQµaH T-Cell

Ù LaMp UsuIt T aMgBIr Rb ePT en He ZVIRb tik mµk ñ úgp ø Úv ep Sg> Kñ a;- T-Cell b Mp ø ajBYk antigen

- cMEN k É B-Cell p l it antibody


tamKImICIv³ eKBnül;Ù eb I adenosine deaminase Kµan sk mµPaBeT en aH v anwgeZVIeGay deoxyadenosine

RtUv r gRb tik mµp UsVr Il k mµEdl b N þal eGayk Mhab ´ dATP ek In eLIgr hUt 5 0 dgÙ dATP eT Ar ar aMgsk mµPaB ribonucleotid reductase nigb næ yk ar sMeyaKé n dNTP d*é T eT [tÙ en H KWCak ar b J Ä b ´é n k ar sMeya K DNA nigk ar lUt l asé n ek a si k a e hIy ek a sik aE dl sM eya KLaMp UsuIt KWCaCal ik aEdl deoxyadenosine RtUv r gRb tik mµp UsVr Il k mµsk mµCageT


Ù ribonucleotide reductase

C MrujRbtik m µe rduk m µénribonucleotidee dIm |Ibe g,Itdeoxyribonucleotide

vdþBuyrInnuyekøGUTItÙ e lak John Lowenstein: nb gØ ajza v d þBuy r Innuy e kø GUTIt(purinenucleotid cycle) m ansar ; sMxanN ase nAkñ úg e m tabUlIsénsacd uM

Ù kar e kIne LIg énskmµPaBsac´d uM: nTam Tar kar e kIne LIg énskmµPaBv d þGasuItsuIRTicE d r


karxVHGg;suIm AMP deaminaseqab;ht;Gs;kMlaMg

Ù e d Im|Ie Gay v d þGasuItsuIRTicskmµe LIg sac´d uMRtUv kar y k fumarate BIv d þBuy r Innuy e kø GUTItb J ©Úle TAkñ úg plitplBak´kN þalénv d þGasuItsuIRTic

Ù skmµPaBGg ´suIm TaMg bIénv d þBuy r Innuy e kø GUTItkñ úg sacd uMe kIne LIg x¬sCagCalikae pSg >e T[t

Ù buK<lE d lTTYlm r tkBIO Buk- mþay m knUv kar xVH AMP deaminaseÙ buK<lE d lTTYlm r tkBIO Buk- mþay m knUv kar xVH AMP deaminase

e nAkñ úg sac´d uM KWqab ´e n] y htGskMlaMg


rlaksnøak; :RbRKIv : Ù cMe J Hm nusSnig stVe pSg >e T[t KWGasuItGu)y r ic‘uric acid) Caplitplcug e Rkayénkar bME b k: sBuy r In nig RtUv : nb e J ©je calm ke RkAtam Twke namÙ kale bIkMhab ´r b sGasuItGu)y r ice LIg x¬s b N þale Gay m anCMgWr laksnø ak‘Rb RKIv ’Ù e r aKlk¡N; r b sv a KWkar QWxø aMg mYy r Me Bce nAkñ úg snø akÙ b J Ø ae nHe kIte LIg e d ay kMN ksüÚd üÚm Gu)y r¨ at‘ minr layÙ e r aKlk¡N; r b sv a KWkar QWxø aMg mYy r Me Bce nAkñ úg snø akÙ b J Ø ae nHe kIte LIg e d ay kMN ksüÚd üÚm Gu)y r¨ at‘sodium urate)minr lay


karBüa)alQWsnøak;Ù kar QWsnø ak´GacBüa: le d ay e RbIZatub gÁak´‘inhibitor’ énxanthineoxidase (allopurinol)

Ù TMr g ´mU e lKulr b s allopurinol KWRse d ] g nwg hypoxanthine

Ù allopurinol e nACab ´nwg Gg ´suIm e hIy k*e ZVIe Gay Gg ´suIm e naHGskmµÙ allopurinol b nÆ Úr e r aKlk¡N; énCMgWRb RkIv Kwv ab næ y e l|} nén

kar sMe y aKGasuItGu)y r ickñ úg e Ble naHe ZVIe Gay hypoxanthine nigxanthine E d lCamU e lKulr lay e kIte LIgxanthine E d lCamU e lKulr lay e kIte LIg


Ù CMgWe nHGace kItm anr hUtd l3 nak´kñ úg 1000nak´ CaBie sscMe J Hbur se d ay sar m ankar r Mxanénkar b e J ©jGasuItGu)y r ic

RKYstMrgenam Ù süÚd üÚm Gu)y r ¨ at r WGasuItGu)y r ic Gackke nAkñ úg tMr g e nam nig bMBg e nam

CaTMr g ´RKab ´zµE d lb N þale Gay xUckMr g e nam

Ù mUle htu KWkar xVHén hypoxanthine guanine phosphoribosyl transferase

(HGPRT) E d le ZVIe Gay e kInén 5-phosphoribosyl pyrophosphate (PRPP) r Yck*CMr ujkar sMe y aKGasuItGu)y r ice lIslb ´

Hypoxanthine + PRPP HGPRT IMP + PPi


2- karbMEbkBIrImIDInÙ BIr ImIDInnuy e kø GUTIt‘pyrimidine nucleotide)RtUv bME lg e TACa: s

r b sv aÙ Rb tikmµRb RBwtþe TAe d ay sar e d pUsVr Ilkmµ e d GamInkmµ nig kar kat

pþac´sm¬&nÆ Kø úy kUsuIt r Yce kIt: n uracil nig thymine e nAkñ úg e zø ImÙ lTÆ plcug b J ©b énBIr ImIDIne m tabUlIsKWGamIN UGasuIt(alanine)Ù lTÆ plcug b J ©b énBIr ImIDIne m tabUlIsKWGamIN UGasuIt(alanine)

r YcRtUv bME lg e TACa malonyl-CoA nig methyl-malonyl-CoA

tam r y ; Rb tikmµe pÞ r b g<úMGamIn r YcRtUv r Mlay b nþe T[t


pøÚvénkarbMElgBIrImIDIn

UMPnig dTMP RtUv : nb MEl g e dayG g´ suI m mYy.k ar b MEl g dTMP emIlk ñ úgv g´Rk ck


III- karsMeyaKnuyekøGUTIt-kUGg;suIm (nucleotide-coenzyme)


1-karsMeyaKnuyekøGUTIt-kUGg;suIm

(nucleotide-coenzyme)

Ù p ø Úv é n k ar sMeyaK NAD+ nigNADP+ ecjm k BIv It amInnicotinatenig Nicotinamidnicotinatenig Nicotinamid

k *dUcCaBIp l it p l é n k ar r Ml aytryptophan


2- flavin-coenzyme (FAD)

Ù FADRtUv : nsMe y aKe cjBI riboflavin


8. nucleic acid metabolism [compatibility mode]

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Transcript of 8. nucleic acid metabolism [compatibility mode]