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第六章核酸（Sixthchapternucleicacid）SixthchapternucleicacidNucleicacidsaregeneticmaterialIn1868,Miesher.acidisolatedfromthenucleiofpuscellsinSwitzerlandwassolubleinalkalisandnotsolubleindiluteacids.Circumstantialevidence:DNAlevelsareessentiallyconstantindifferenttypesofcellsatdifferentgrowthstagesofthesamespecies.Directevidence:T2phageDNAinfectedwithE.coliThephageproteinwaslabeledwith35S,infectedwithE.coli,andinfectedwithE.coliby32PlabeledphagenucleicacidThedistributionofDNAandRNA(DNAinthenucleusandRNAoutsidethenucleus).Section1chemicalcompositionofnucleicacidsNucleicacidisalinearpolynucleotide,thebasicunitofwhichisnucleotides.Structurelevel:nucleicacidnucleotideNucleosidephosphatePentosebaseTherearetwokindsofpentosethatmakeupnucleicacids:D-riboseandD-2-ribose.Thus,nucleicacidscanbedividedintotwokinds:RNAandDNAP330Table5-1thebasicchemicalcompositionoftwotypesofnucleicacidsBase1.purinebase:adenineguanine2.pyrimidinebases:cytosine,uracil,thymineP331structureformula3.modifiedbaseThereisalargeamountof5-methylcytosineinplants.InE.coliphage,5-hydroxymethylcytosineinsteadofC.Rarebase:morethan100species,mostofwhicharemethylatedproducts.DNAconsistsofA,G,C,andTbases.RNAconsistsofA,G,C,andUbases.TwonucleosideNucleotidesarecondensedfrompentoseandbases,C1onthesugarring,orN1ofthepyrimidinebase,ortheN9connectionwiththepurinebase.NucleosidesinnucleicacidsarebetanucleosideP332structuredadeninenucleosidecytosinenucleosideDNA'spentoseis:deoxyriboseRNA'spentoseisriboseThreenucleotidesInnucleoside,pentoseC3andC5hydroxylgroupsareesterifiedbyphosphoricacidtoproducenucleotides.1,constitutethenucleotideofDNAandRNAP333,table5-32.IntracellularfreenucleotidesandtheirderivativesNucleoside5'-polyphosphateATP,GTP,CTP,ppppA,ppppGItplaysanimportantroleinenergymetabolism,metabolismandregulation.ThecyclicnucleotideCAMP(3,5,-cAMP),cGMP(3,5,-cGMP)Theyactassecondmessengersofthehormoneintheplasmamembrane,andcAMPregulatesglucosemetabolismandlipidmetabolismincells.Nucleoside5'polyphosphate3'-polyphosphatePpGpppppGppppAppNucleotidederivativeHSCoA,NAD+,NADP+,FADandothercofactors.GDP-galactose,GDP-andglucoseareactiveglycosyldonorsforglycoproteinbiosynthesis.SecondsectionDNAstructureLevel1:molecularlinkageandsequenceofDNAnucleotides.Twostage:doublehelixstructureformedbyhydrogenbondsbetweentwostrandsofDNA.Threestage:DNAdoublechainsarefurtherfoldedandcurledtoformconformation.I.TheprimarystructureofDNATheprimarystructureofDNAisalinearpolymerof4nucleotides(dAMP,dGMP,dCMP,dTMP)linkedby3/,5/-,phosphatetwoesterbonds.The3/and5/-phosphatetwoesterbondsarethebackbonestructuresofDNAandRNA.P334,figure5-1Writingmethod:5/=3/:5'-pApCpTpG-3'or'5'...ACTG...3(inDNA,3/-OHisusuallyfree)InDNAmolecules,theinvariantskeletoncomponent,thephosphatetwoesterbond,isgraduallyomitted,andtheorderofthebasesthatreallyrepresentthebiologicalsignificanceofDNAistheorderofthebases.GeneticinformationisstoredinthebasesequenceofDNA,andbiologicaldiversityliesintheprecisesequenceofthe4nucleotidesoftheDNAmolecule.Two,DNA'stwostagestructureIn1953,WatsonandCrickproposedadoublehelixmodelofDNAbasedontheChargafflawandtheXraydiffractiondataofDNAandNasaltfibers.1,Watson-CrickdoublehelixstructurefoundationChargafflaw,1950A.inallDNA,A=T,G=C,andA+G=C+T.P334table5-4.ThebasecompositionofB.DNAhasaspeciesspecificity,thatis,DNAofdifferentorganismshasitsownuniquebasecomposition.ThebasecompositionofC.DNAhasnotissueororganspecificity.D.,age,nutritionalstatus,environmentandotherfactorsdidnotaffectthebasecompositionofDNA.XraydiffractionanalysisofNasaltfiberandDNAcrystalofDNA.Relativehumidity92%,DNAsodiumsaltcrystallization,B-DNA.Relativehumidity75%,DNAsodiumsaltcrystallization,A-DNA.Z-DNA.DNAinorganismisB-DNA.Franklin'sjobDoublehelixstructuremodelof2andWatson-CrickP335,figure5-2A.twoantiparallelpolynucleotidechainsaroundthesameaxisphasewinding,formingaright-handeddoublehelix,5'-3',another3'-5'B.purineandpyrimidinebasesarelocatedontheinsideofthedoublehelix,withphosphateandriboseontheoutside.Phosphoricacidandribosearelinkedtoeachotherby3/,5/-,andphosphatetwoesterbonds,formingthebackboneofDNAmolecules.Width1.2nmwide0.6NmBigditchditchDeep0.85nmdeep0.75nmC.helixaveragediameter2nmEachcoilcontains10nucleotidesBasestackingdistance:0.34nmPitch:3.4nmD.twonucleotidechainsthatdependonachainofhydrogenformedbetweenbasesofeachother.Thebaseplaneisperpendiculartothespiralaxis.A=T,G=CP336,figure5-4Theprincipleofbasecomplementationisofgreatbiologicalimportance.ThemolecularbasisofDNAreplication,transcriptionandreversetranscriptionisbasecomplementation.3,stabledoublehelixstructurefactorThebaseaccumulationforce(mainfactor)formshydrophobicenvironment.Basepairinghydrogenbonds.ThemoreGCcontent,themorestable.Thenegativechargeonthephosphategroupformsanionicbondwiththecationsinthemediumorthepositiveionsofthehistones,neutralizingtherepulsionbetweenthenegativechargesonthephosphategroupandcontributingtothestabilizationoftheDNA.Thebaseisinthehydrophobicenvironmentofdoublehelixandcanbeattackedbysmallwater-solublemolecules.Theheterogeneityandpolymorphismo