生物化学(英文版)biochemistry-chapter1英

Biochemistry,YonggeWuSchoolofLifeScienceNationalEngineeringLaboratoryforAidsVaccineJilinUniversity,WhatisBiochemistry?,Biochemistryisthestudyofthemoleculesandchemicalreactionsoflife.Itisthedisciplinethatusestheprinciplesandlanguageofchemistrytoexplainbiologyatthemolecularlevel.,CourseOrganization,Staticpart:,Dynamicpart:,Tointroducestructureandfunctionofbiomolecules(proteins,nucleicacids,carbohydrates,lipidsetc.),Tointroducechemicalactions,coursesandreactionsinlivingsystems,thatisMetabolism.,ProteinEnzymeCarbohydrateLipidNucleicAcidVitaminHormone,Staticbiochemistry,Dynamicbiochemistry,MetabolismandenergyCarbohydratemetabolismLipidmetabolismProteinmetabolismNucleicacidmetabolismGeneticinformationtransmission,Contentsofbiochemistry,TheTextbooks,PrinciplesofBiochemistry(3rdEdition)H.R.Horton等主编，科学出版社2003.4生物化学（第三版）王镜岩、朱圣庚等主编，高等教育出版社2002.9,ContentsofBiochemistry(1)-Thissemester,Chapter1IntroductiontoBiochemistryChapter2WatersChapter3AminoAcidsandPrimaryStructuresofProteinsChapter4Proteins:Three-DimensionalStructureandFunctionChapter5PropertiesofEnzymesChapter6MechanismsofEnzymesChapter7CarbohydratesChapter8LipidsandMembranesChapter9CoenzymesandVitamins,Chapter1IntroductiontoBiochemistry,1.1Briefhistoryofbiochemistry1.2Whatarethequestionsforbiochemiststoanswer?1.3Biochemistryandotherdisciplines.1.4Applicationofbiochemistry1.5Basicpropertiesoflivingsystems,1.1BriefhistoryofBiochemistry,Period1OriginPhasethelatecentury18.,Period2DevelopingPhaseFromtheforepartto40sofcentury20.,Period3RapidDevelopmentPhaseFrom1950stopresent.,1780sAntoineLaurentLavoisier(French):Combustionofacandleissimilartothe“respiration”ofanimals,asbothneedO2.Forthefirsttimeaphysiologicalprocesswasexplainedwithreferencetoanonlivingmechanism.Disaffirming“ThePhlogistonTheory”,Period1OriginPhaseModernBiochemistrywasborninthelatecentury18asthedevelopmentofChemistryandPhysiology.,In1838,J.J.Berzelius(Swedenchemist)namedtheterm“Protein”whichwasfromGreek“proteios”,meaning“mostimportant”.Buthetheorized“Vitalismtheory”.,In1828，F.Whler(GermanyChemist，1800-1882）showedbysynthesizingureafromammoniumcyanatethatcompoundsfoundinlivingorganismscouldbemadeinthelaboratoryfrominorganicsubstrances.Accordingly,herejectedthe“Vitalismtheory”,V.Liebig(GermanyChemist，18031873）wasoneoffoundersofBiochemistry.NutrientoffoodweredividedintoCarbohydrate,LipidandProtein.Proteinsfromhumanandanimalweresameonstructureandproperties.Proteinwasnecessaryforlife.CarbohydratecanbeentransformdtoLipid.CarboncanbeentransformdtoCO2byoxygenation.Nitrogencanbeentransformedtourea.Broughttheterm“Metabolism”forthefirsttime.Fermentwasasolubleprotein.Itsfunctiondidnotdependontheintegralityofyeastcell.,LouisPasteur(Frenchmicrobiologist，1822-1895)His3majorscienceachievements：1.Disaffirmed“Autogenetictheory”.Invent“pasteurism”。2.Everyinfectiousdiseasewasproducedfromamicroorganism.SalvationFrenchsilkindustryasfoundainvasionbacterialofsilkworm.3.InventedRabiesvaccine.Buthethoughtmistakenlythatfermentcanonlyworkinlivingyeastcell.,1890s,E.Buchner(German):Yeastextract(nolivingcell)canfermentsugartoalcohol.Enzymecanfunctionwhenremovedfromthelivingcell.Rejected“vitalismtheory”.,In1878,W.Kuhnecalledthem“Enzyme”forthefirsttime.In1883,AnselmePayen(Frenchchemist)discoverAmylase.“-ase”waspostfixofenzymes.HeisolatedCelluloseandnamedit.“-ose”waspostfixofcarbohydrates.,In1877,F.Hoppe-Seyler(Genmandoctor)calledtheterm“Physiologicalchemistry”forthefirsttime.Originated“JournalofPhysiologicalchemistry”IsolatedHemeandobtaineditscrystal.,In1868,JFMiescher(Swedendoctor)isolated“nuclein”tobethefounderofnucleicacid.In1888,A.Kossel(Germanbiochemist)proved“nuclein”wasacomplexofproteinandnucleicacid.Isolated4kindsofbases.Researchedthestructureofnucleicacid.,In1911,P.A.T.Levineprovedthestructureofsugarfromnucleicacid,andnamedit“Ribose”.Found2kindsofdiffenentnucleicacidRNAandDNA.Foundednucleotide.Butmademistakenly“Fournucleotidehypothesis”.,EmilFischer(Germanchemist)wasoneoffounderofBiochemistry.In1900s,hetheoryzed“peptidebondtheory”onproteinstructure.Inventedthemethodofpeptidesynthesis.In1894,hetheorized“Lock-Keytheory”ofEnzyme.In1903,C.A.Neuberg(German)namedtheterm“Biochemistry”.Establishedthe“Glycolysistheory”.,Period2DevelopingPhaseFromtheforepartto40sofcentury20,thechemicalessenceofEnzymeandbiomolecularmetabolismpathwayswerediscoveredwiththetechnologyimprovementofpurificationaschromatograpy,electrophoresis,fluorescenceanalysis,isotope,ultracentrifugeandelectronicmicroscope.,In1926,J.B.Sumner(Americanchemist):crystalliztionofurease.Heproveditisaprotein.,1912-1933,Biologicaloxidationwasresearchedthoroughly.1930s,provedthatEnzymeareprotiens.In1937,A.Krebs(Englishbiochemist)discovered“UreaCycle”and“TricarboxylicAcidCycle”(TCACycle,KrebsCycle).In1940s,glycolysispathwayandphoto-synthesiswerediscovered.,DiscoveryofVitamin:In1886,C.Eijkman(Netherlanddoctor)In1906FrederickHopkins(Englishbiochemist)In1911,C.Funk(Polandchemist):VataminB1,Funknamedit“Vitamine”,meaning“Vitalamine”.Lateritwasrenamedas“Vitamin”.In1912，HopkinsandFunkputforward“vitamindeficiencyhypothesis”.,Discoveryofhormone:In1902,EHStarling(Englishphysiologist)andWMBaylissdiscoveredSecretin(促胰液素),In1922,F.G.Banting(Canadianphysiologist)andC.H.BestpurifiedInsulin.DNAcarriesgeneticinformation:In1928,FGriffith(English)-theexperimentofbacteriatransformation.In1944,O.T.Avery(Canada)theexperimentofbacteriatransformation.In1952,A.D.HerskeyandM.Chase-T2phage.,Bacteriatransformation,1.ThecolonyofWild-typeStreptococcuspneumoniaeissmooth(TypeS).Thecolonyofamutantisrough(TypeR).Theirdifferenceisonformationofcapsule.,Griffithsexperiment,Conclusion:,Asubstancefromadeadtoxicbacteriumcantransformintoanotherlivingnontoxicbacterium.Theprocesswascalled“Transformation”.Thetransformedsubstancewasnamed“tranformingfactor”.,Averysexperiment:,Conclusion:,TheevidencepresentedsupportsthebeliefthatanucleicacidofthedesoxyribosetypeisthefundamentalunitofthetransformingprincipleofPneumococcusTypeIII.(OSWALDT.AVERY,M.D.,COLINM.MAcLEOD,M.D.,ANDMACLYNMcCARTY,*M.D.StudiesOnTheChemicalNatureOfTheSubstanceInducingTransformationOfPneumococcalTypesInductionOfTransformationByADesoxyribonucleicAcidFractionIsolatedFromPneumococcusTypeIII.TheJournalofExperimentalMedicine.February1,1944,Vol.79,No.2,pp.137-158),In1946,G.Beadle(Americanbiologist)andE.Tatumprovedthatagenecontrolsthesynthesisofaenzyme.Andtheytheorized“Onegeneoneenzymehypothesis”.,Period3RapidDevelopmentPhaseFrom1950stopresent.Thecomposition,sequence,structureandfunctionofbiologicalmacromolecularsuchasprotein,enzymeandnucleicacidwereresearchedprofoundly.Chemicalsynthesistechnologywasbeengreatlydeveloped.Geneticengineeringwasestablished.,In1950,Paulingputforward-Helixofproteinsecondarystructure.In1953,J.Watson&F.Crickestablished“DNADoubleHelixModel”.ItisthemilestoneofmodernMolecularBiology.In1958,F.Crickputforward“centraldogma”.In1966,Nirenberg&Khoranadecodedgeneticcode.,R.Franklin,F.Crick,J.watson,M.Wilkins,In1953and1975,F.SangerwontwoNobelPrizesastheinventionofmethodsofproteinsequencingandnucleicacidsequencingrespectively.In1961,F.JacobandJ.Monodputforward“operontheory”.,TheinventorofDNAsequencing,doubleNobelprizewinnerFredSanger,In1970,H.TeminandD.Baltimorefoundreversetranscriptasemeantime.,In19721973,PaulBergandCohenetc.establishedDNArecombinanttechnologyresultinginbirthof“GeneticEngineering”.,Basicprocedureofgenecloning,In1975，E.SoutherninventedmolecularhybridizationtoprobeDNA”SouthernBlot”.In1982and1983，T.CechandS.Altmandiscovered“ribozyme”respectively.In1985，K.Mullisinvented“PolymeraseChainReaction(PCR)”.,Cech,Altman,Mullis,HumanGenomicProject(HGP):In1986,aNobelprizewinnerR.DulbeccopublishedapaperinSciencetofirstproposeHumanGenomicProject.In1991,HGPbeganitsresearchplanof15years.OnJune26,2000,theworkingdraftofHumangenesequencewaspublished.,In1997，sheepDolly-thefirstmammaltobeclonedfromanadultcellbyI.Wilmut.,I.Wilmut-AusurperofGodspatent.,CloningOrgan,CloningOrganism,Genetherapy:In1980,MartinClinefromUniversityofCaliforniaatLosAngelestestedhisgenetherapyideasonpatientswithThalassemia(地中海贫血症),butfailedtohelphissubjects.OnSep.14,1990,W.F.AndersoncompletedsuccessfullyfirstgenetherapyonA4-year-oldgirlnamedAshanthiDeSilvawithadenosinedeaminase(ADA)genedeficiency.Itwasamilestoneofhumangenetherapy.OnSep.17,1999，A18-year-oldteenagerJesseGelsingerwithornithinetranscarboxylasedeficiency(OTCD)receivedthegenetherapy.Fourdayslater,hewasdead.,AchievementofChinascientistsonBiochemistry:In30s，XianWuputforward“Denaturetheoryofprotein”.Cooperatedwithseveralteamsfirstonchemicallysynthesisbovineinsulinin1965andyeastalaninetransferRNAin1983respectively.1%sequencingDNAofHGPwerecompletedbyChina.Genetherapymedicinep53(Gendicine,今又生)wasmarke