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1、CHAPTER29BIOSYNTHESISOFNUCLEOTIDESNucleotidesplaykeyrolesinthefollowingbiochemicalprocesses:AsactivatedprecursorsofDNAandRNA核酸前体Theirderivativesareactivatedintermediatesinmanybiosyntheses,e.g.UDP-GlcandCDP-DAGandS-AMet活性中间物ATPisauniversalcurrencyofenergyinbiologicalsy
2、stems,GTPpowersmanymovementsofmacromolecules能量通用形式Adeninenucleotidesarecomponentsof3majorcoenzymes:NAD+,FAD,andCoA辅酶Asmetabolicregulators,e.g.cAMPandATP代谢调节物Nucleotidesaresynthesizedfromsimplebuildingblocks(denovosynthesis从头合成)orbytherecyclingofpreformedbases(salvagesy
3、nthesis节约利用途经)Purines(Pur.)andpyrimidines(Pyr.)arebuiltdenovofromAA,FH4derivatives,NH4+andCO2ThePRmoietyofribonucleotidescomesfromPRPP,anactivateddonorDeoxyribonucleotidesaresynthesizedbyreductionofribonucleotides(dNDPfromNDP)Finally,dTMPisformedbymethylation甲基化ofdUMP(
4、UMP→dUMP→dTMP)Nucleotideanalogsarevaluabledrugsinthetreatmentofcancers(P753),viralinfections,autoimmunediseases,andgeneticdisorderssuchasgout痛风症(P757)ThepurineringissynthesizedfromAA,FH4derivatives,andCO2ThePurRingisassembleddenovofromseveralsimpleprecursors1.Gly(C-4,C
5、-5,N-7)2.Asp(N-1)3.Gln(N-3,N-9)两次FH4(C-2,C-8)两次CO2(C-6)PRPPisthedonorofthePRunitofnucleotides(Nt)PRPPprovidesPRportionforthesynthesisofPurandPyrNt,justasforthatofTrpPRPPissynthesizedfromATPandR-5-P,whichisprimarilyformedbyPPPPRPPsynthetasecatalyzesthetransferoftheβ-γpy
6、rophosphorylgroupofATPtoC-1ofR-5-PPRPPhasanα-configurationatC-1,theactivatedcarbonatomα-构型ThePurringisassembledonPRThecommittedstepinthedenovosynthesisofPurNtistheformationof5-phosphoribosylamine(5-磷酸核糖胺)fromPRPPandGlncatalyzedbyamido-phosphoribosyltransferase酰胺磷酸核糖转移酶
7、Theamidegroup(酰胺基)fromGlndisplacesthePPigroupattachedtoC-1ofPRPPTheconfigurationatC-1isinvertedfromαtoβinthisreactionTheresultingC-NglycosidicbondhasβconfigurationthatischaracteristicofnaturallyoccurringNtβ-构型是天然存在的核苷酸中的糖苷键的构型Thisreactionisdrivenforwardbythehydrolysiso
8、fPPiPRPP→phosphoribosylamine磷酸核糖胺→glycinamideribonucleotide甘氨酰胺核苷酸→formylglycinamideribonucleotide甲酰甘氨酰胺核苷酸→formylgly