生物化学理论课件中科大核苷酸代谢PPT文件格式下载.ppt
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生物化学理论课件中科大核苷酸代谢PPT文件格式下载.ppt
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核苷酸代谢核苷酸代谢1,1,背景知识背景知识22,核苷酸的合成,核苷酸的合成33,核苷酸合成异常与疾病,核苷酸合成异常与疾病44,核苷酸合成代谢的调节,核苷酸合成代谢的调节55,核苷酸的降解,核苷酸的降解66,核苷酸代谢和化疗,核苷酸代谢和化疗77,核苷酸类似物与遗传标记核苷酸类似物与遗传标记ThemostcommonnucleotidesfoundincellsAMPCMPGMPUMPADPCDPGDPUDPATPCTPGTPUTPdAMPdCMPdGMPdTMPdADPdCDPdGDPdTDPdATPdCTPdGTPdTTPcAMPdUMPdUDPdUTP碱基碱基核苷酸核苷酸核苷核苷FrancisHarryFrancisHarryComptonCrickComptonCrickb.1916b.1916d.2004d.2004JamesDeweyJamesDeweyWatsonWatsonb.1928b.1928MauriceHughMauriceHughFrederickFrederickWilkinsWilkinsb.1916b.1916d.2004d.2004YettherewasoneotherpersonwhosetrulyessentialcontributiontothisdiscoverycouldnotberecognizedbyYettherewasoneotherpersonwhosetrulyessentialcontributiontothisdiscoverycouldnotberecognizedbytheNobelCommitteein1962.ThatpersonwasRosalindFranklin.theNobelCommitteein1962.ThatpersonwasRosalindFranklin.AfterRandallpresentedFranklinsdataandunpublishedconclusionsataroutineseminar,aspectsofherAfterRandallpresentedFranklinsdataandunpublishedconclusionsataroutineseminar,aspectsofherresultswereinformallycommunicatedtoWatsonandCrickbyMauriceWilkinsandMaxPerutz,withoutherorresultswereinformallycommunicatedtoWatsonandCrickbyMauriceWilkinsandMaxPerutz,withoutherorJohnRandallsknowledge.ItwasWatsonandCrickwhoputallthepiecesofthepuzzletogetherfromavarietyJohnRandallsknowledge.ItwasWatsonandCrickwhoputallthepiecesofthepuzzletogetherfromavarietyofsourcesincludingFranklinsresults,tobuildtheirultimatelycorrectandcompletedescriptionofDNAsofsourcesincludingFranklinsresults,tobuildtheirultimatelycorrectandcompletedescriptionofDNAsstructure.TheirmodelforthestructureofDNAappearedinthejournalNatureinApril,1953,alongsidestructure.TheirmodelforthestructureofDNAappearedinthejournalNatureinApril,1953,alongsideFranklinsownreport.Franklinsownreport.Watson,J.D.andF.H.Crick.1953.Astructurefordeoxyribosenucleicacids.Nature171:
@#@737-738.Wilkins,M.H.F.,StokesA.R.andH.R.Wilson.MolecularStructureofDeoxypentoseNucleicAcids.Nature171:
@#@738-740FranklinR.andR.G.Gosling.1953.MolecularConfigurationinSodiumThymonucleate.Nature171:
@#@740-741B-DNAZ-DNA1,1,背景知识背景知识22,核苷酸的合成,核苷酸的合成33,核苷酸合成异常与疾病,核苷酸合成异常与疾病44,核苷酸合成代谢的调节,核苷酸合成代谢的调节55,核苷酸的降解,核苷酸的降解66,核苷酸代谢和化疗,核苷酸代谢和化疗77,核苷酸类似物与遗传标记核苷酸类似物与遗传标记DenovoDenovosynthesissynthesisofnucleotidesbeginswiththeirmetabolicofnucleotidesbeginswiththeirmetabolicprecursors:
@#@precursors:
@#@aminoacids,ribose5-phosphate,COaminoacids,ribose5-phosphate,CO22,andNH,andNH33.肌苷酸、次黄苷酸肌苷酸、次黄苷酸磷酸核糖焦磷酸磷酸核糖焦磷酸氨甲酰磷酸氨甲酰磷酸Referencepathway磷酸核糖焦磷酸磷酸核糖焦磷酸ThebiosyntheticoriginsofThebiosyntheticoriginsofpurinepurineringatomsringatomsSynthesisofSynthesisofInosineInosinemonophosphsatemonophosphsate(IMP,(IMP,肌苷酸肌苷酸/次黄苷酸次黄苷酸)SynthesisofGMPandAMPSynthesisofGMPandAMP腺苷琥珀酸腺苷琥珀酸延胡索酸延胡索酸黄苷酸黄苷酸肌苷酸肌苷酸/次黄苷酸次黄苷酸RegulatorynetworkoftheRegulatorynetworkofthepurinepurinepathwaypathwaySynthesisofUMPSynthesisofUMPSynthesisofCTPSynthesisofCTPSyntheticpathwaystothyminenucleotidesSyntheticpathwaystothyminenucleotidesdCMPdeaminaseDeoxycytidinekinaseThymidylatesynthaseThymidinekinaseThymidinekinasedUTPasedTTPdTTPdCTPdCTPRegulatorynetworkofRegulatorynetworkofpyrimidinepyrimidinesynthesissynthesisOverviewofOverviewofdNTPdNTPbiosynthesisbiosynthesisReutilizationofpurineandReutilizationofpurineandpyrimidinepyrimidinebasesbases1,1,背景知识背景知识22,核苷酸的合成,核苷酸的合成33,核苷酸合成异常与疾病,核苷酸合成异常与疾病44,核苷酸合成代谢的调节,核苷酸合成代谢的调节55,核苷酸的降解,核苷酸的降解66,核苷酸代谢和化疗,核苷酸代谢和化疗77,核苷酸类似物与遗传标记核苷酸类似物与遗传标记ImmunodeficiencyandDefectivePurineCatabolismImmunodeficiencyandDefectivePurineCatabolism1.1.Personswithseverecombinedimmunedeficiency(Personswithseverecombinedimmunedeficiency(SCIDSCID)aretotally)aretotallyunabletomountanimmuneresponsetoantigens.BoththeBandTunabletomountanimmuneresponsetoantigens.BoththeBandTlymphocytesareaffected.Thediseasearisesfromaninheritedlackoflymphocytesareaffected.Thediseasearisesfromaninheritedlackofaadegradativedegradativeenzyme,enzyme,adenosineadenosinedeaminasedeaminase(ADA).(ADA).2.2.ThereactionshownThereactionshownbelowbelowillustratesthepathwaysaffected.illustratesthepathwaysaffected.3.3.LackofLackofADAADAallowsallowsdeoxyadenosinedeoxyadenosinetriphophosphatetriphophosphate(dATPdATP)totoaccumulateaccumulatefromthedegradationofDNA.fromthedegradationofDNA.4.4.HighHighdATPdATPlevelsinhibitproductionoftheotherlevelsinhibitproductionoftheotherdNTPsdNTPsneededforneededforDNAreplicationbecauseoftheirallostericeffectsontheenzymeDNAreplicationbecauseoftheirallostericeffectsontheenzymeribonucleotidereductaseribonucleotidereductase.5.5.WhitebloodcellsarethemostaffectedbylackofWhitebloodcellsarethemostaffectedbylackofADAADA.W
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