生化-郑利民课件生化引论－郑利民

,BiochemistryI,上课老师及其联系方式：郑利民教授；生化系主任Tele-mail:Ls110李国富副教授Tele-mail:Ls108欢迎大家就课程发表您们的想法和意见,参考课本：1.LehningerPrinciplesofBiochemistry2.Biochemistry:FifthEditioninternationaledition(J.M.Berg,etal)3.王镜岩，生物化学第三版，2002高教出版社,课件(slides)会留在计算机中；课前预习和课后及时复习,Wonderfulworld：GardenofEden,DiversityandUnity,Amazing?!,DefinitionofBiochemistry,Biochemistryisthechemistryoflife.Thestudyofthemolecularbasisoflifeandtheinteractwitheachotherorunderstandinglifephenomenainchemicalterms.Thecombinationofbiologyandchemistryortheapplicationofchemicalprinciplestounderstandbiology.,TheChemicalUnityofDiverseLives,Livingorganismsvs.inanimateobjectschemicalcomplexityandorganizationuseenergyinasystemicwayself-replicationandself-assemblyBiochemistryExplains:DiverselivesinunifyingchemicaltermsAllmacromoleculesaremadeofafewsimplecompounds,Musicinourbody!,MainQuestionsforBiochemistryI(thissemester):,Whatarethecompositionandstructureofbio-molecules?Howdothesebio-moleculesactandinteractinlivingorganisms？,Allchemicalprocessassociatedwithorganismsatthemolecularlevel-isolatemoleculesanddeterminetheirstructure-analyzetheirfunctionExample:thestudyofDNAHowlifebeganandevolvedOrganisms:uniformatthemolecularlevelindicate:theyarosefromacommonancestor,Themainobjectivesaretounderstand,1.ProteinStructureandFunction*（蛋白质的结构和功能）2.Enzymes:BasicConceptsandKinetics(酶的基本概念及酶促动力学)3.Enzymes:Catalyticthestructureofproteinsandothermacromolecules;theoriesaboutmoleculardisease,suchassickle-cellanemia.,SomeofNobelLaureatesinthehistoricaldevelopmentofBiochemistry,Krebs:CitricAcidCycle(TCA):animportantwaybywhichthecomplexchemicalprocessesprovidelivingorganismswithhighenergyphosphate.,Sanger:SequencingMethodAminoacidsequencingmethodandthecompletesequenceofinsulin.SangerSequencingMethodforDNA,(OswaldAvery,ColinMacleodandMaclynMcCarry),(有荚膜,S;致病性）,Avery:DNAcarriesgeneticmaterial,（无荚膜,R；非致病性）,S(heat-killed)Mouselives,毒力株经加热灭活后会失去其致病性,R+S(heat-killed/extracts)Mousedies,结果小结和分析（背景：以往认为蛋白质携带遗传信息）,有荚膜的活细菌（S）：具致病性；无荚膜的活细菌（R）：无致病性S菌株加热灭活后：无致病性灭活后的S菌株活细菌R：具致病性！提示S菌株中的遗传信息被导入活细菌R该遗传信息对热不敏感，不是蛋白质未知的物质携带了遗传信息！,DNAcarriesthegeneticinformation,1869,Miescherisolatesnuclei,1944,AverydiscoversthatDNAcarriesthegeneticmaterial,1953,WatsonandCrickproposethedouble-helicalstructureofDNA,VariousprocessconcernedwithDNA.ex.semi-conservativereplication.,DNA,RNAandProteinsynthesis,S.OchoaanddoubleortriplebondsbetweentwoCatoms.CovalentlylinkedCatomscanformdifferentstructures（linear,branched,orcyclic）addingfunctionalgroupsconferringspecificactivitiestothemolecules.,Versatilityofcarboninformingcovalentbonds,Organiccompounds:Moleculescontainingcovalentlybondingcarbonbackbones;e.g.alcohols,amines,aldehydes(醛),ketones,羧基,巯基,etcMostbio-moleculesareorganiccompounds.“C”:tetrahedralarrangementofitsfoursinglebonds.C-Csinglebondshavefreedomofrotation,butnotdoublenortriplebonds.Nootherchemicalelementhasthecapacitytoformmoleculesofsuchwidelydifferentsizes,shapes,withvarietyoffunctionalgroups,Mostbiomoleculescanbeconsideredtobederivedfromhydrocarbonshydrophilicinteractionsbetweenbiomolecules,Hydrocarbons,fisher,Ball-and-stick,Spacefilling,Bio-moleculeshave3-Dstructures,Bio-moleculeshave3-Dstructures,ThespecialfeatureoforganiccompoundsisNOTtheircompositionsbutthewaytheiratomsarecombined(structures,1820s)Corollary:twosubstancesmayshowthesamechemicalformulabutphysicallyandchemicallydifferentmaterials(differentstructuresandfunctions).,Conventionusedforconfiguration,Lightabsorbingpigmentinrhodopsinanintegralmembraneprotein,Chiral：手性,Interactionsbetweenbio-moleculesarestereo-specific,Betweenpairsofenantiomers对映(结构)体：usuallyonlyoneformisbiologicallyactive.L-aminoacids(S)arefoundinproteinsD-glucose(R)isbiologicallyactiveOnlyonechiralformisgeneratedinlivingcellsduetoenzymespecificity(1975NobelPrize)Incontrast:thetwoenantiomersareusuallysynthesizedinequalamountsinvitrochemicalsynthesis,Conventionfromorganicchemistry,Chewinggums,绿薄荷,香菜,Twostereoisomersmayhavetotallyoppositebiologicaleffects(e.g.,Chewinggums),Neutralsweet天冬酰苯丙氨酸甲酯,Aspartame,asugarsubstitute;itsstereoisomer,bitter,Fourfamilies:Aminoacids；Sugar；Fattyacids；NucleotidesFunctions:Usedtosynthesizelargermolecules；Havespecialbiologicalfunctions；Involvedincomplexreactionpathways；,MajorClassesofSmallBio-molecules,Fivegeneraltypesofreactionsincells:Oxidation-reduction(氧化还原反应)Internalre-arrangements(isomerization,异构)CleavageSynthesis(increasingorder,thusenergyconsuming)toprovidebuildingmaterials,anabolism.,TheRolesofmetabolism,Extractenergyandreducingpowerfromtheenvironment(生命体通过光合作用和氧化作用从外界吸收能并释放废弃物）,Generation(interconversion)ofallthebiomoleculesforalivingorganism(biosynthesis).（伴随着物质和能量代谢，生物分子间通过分解和合成作用发生互换）,Anabolism合成代谢,Catabolism分解代谢,能源物质,中间代谢产物,废弃物,GeneralFeaturesofmetabolism,linear,branchedorcircularpathways;,Highlyinterconnected各个途径相互交接，形成物与能的网络化交流系统,Tightlyregulatedtoachievebesteconomy精密调控机制保证机体最经济的利用物质和能量,Alllivingorganismsaremadeupofcells,thesmallestunitboththestructuralandfunctionaloflivingmatters.Cellsarecapableofself-reproduction.MostcellsaremicroscopicinsizeEukaryoticcells:5-100mminsize；bacteria:1-2mm;mycoplasma:0.3mm,Cell:FundamentalUnitofLife,Prokaryotic(原核）cells:Lackanucleuse.g.,EubacteriaandarchaeaSimplestructure;Abundantspecializedfunctionssuchasmusclecontractionandnerveimpulseconduction,Plasmamembraneisalipidbilayercomposedoflipidandproteinmolecules,Others：Peroxisomes过氧化物酶体Chloroplasts叶绿体Thecytoskeletonsystemetc,Aroughanalogybetweenthethecellandthehumansociety,Nucleus:thehighestadministrativesection.Mitochondriaandchloroplasts:thepowerplant.GolgiApparatus:thepostofficeCytoskeletonsystem:thehighways(transportation)Lysosomes:therecyclingcenterER:thefactory，training&educationcenterPlasmamembrane:theborderlineLikethesociety,thecytoplasmiscrowded,highlyorganized,anddynamic.,2004年世界十大科技进展新闻是：1.“勇气”&“机遇”号发现火星有水的证据,ItisNOTanaccidentthatlifearoseinassociationwithwater,sincethissubstancehasseveralunusualpropertiesthatsuitstobethemediumoflifeThermalpropertiesSolventcharacteristics,Water:MediumofLife,ThermalProperties:Watersmelting&boilingpointsareexceptionallyhighcomparedwithrelatedmoleculesofsimilarmolecularweight,WatershighheatofvaporizationandhighheatcapacitymakeitaneffectivemodulatorofclimatictemperatureWaterplaysanimportantroleinthethermalregulationoflivingorganismshelpsmaintainanorganismsinternaltemperature,HydrogenbondingisresponsibleforthisanomalousbehaviorEachwatermoleculecanformhydrogenbondswithfourotherwatermolecules,SolventPropertiesofWater,WatersdipolarstructureanditscapacitytoformhydrogenbondsenablewatertodissolvemanyionicandpolarsubstancesSaltsOrganicmoleculeswithionizablegroupsorwithpolarfunctionalgroups,NoncovalentBonding,HydrogenBondsElectrostaticinteractionsVanderWaalsforcesHydrophobicinteractions,HydrogenBonds,ElectrostaticInteractions,ElectrostaticinteractionsoccurbetweenoppositelychargedatomsorgroupsTodeterminetheshapeandfunctionofbiomoleculesThree-dimensionalstructureofproteinHydrationofions,Electrostaticinteractionsbetweenchargedgroupsorpolargroupsonbiomoleculesar