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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
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
Heng Savoeun/2009 14
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
Heng Savoeun/2009 15
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
Heng Savoeun/2009 16
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
Heng Savoeun/2009 17
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
Heng Savoeun/2009 18
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
Heng Savoeun/2009 19
2- e d GuksuIrIbUn uye kø GUTIt ‘deoxyribonucleotide)
Heng Savoeun/2009 20
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)
Heng Savoeun/2009 21
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
Heng Savoeun/2009 22
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
Heng Savoeun/2009 24
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
Heng Savoeun/2009 25
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
Heng Savoeun/2009 26
pø Úv énkar bME lg AMP nige TACaGasuItGu)y r ic
pø Úv énkar bME lg nigGMP e TACaGasuItGu)y r ic‘uric acid)
Heng Savoeun/2009 27
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
Heng Savoeun/2009 28
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
Heng Savoeun/2009 29
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
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