生化生化引論

BiochemistryI上課老師及其聯(lián)系方式：鄭利民 教授；生化系主任Tele-mail:Ls110@李國(guó)富 副教授Tele-mail:Ls108@歡迎大家就課程發(fā)表您們的想法和意見(jiàn).

參考課本：1.LehningerPrinciplesofBiochemistry

2.Biochemistry:FifthEdition internationaledition(J.M.Berg,etal)3.王鏡巖，生物化學(xué)第三版，2002高教出版社課件(slides)會(huì)留在計(jì)算機(jī)中；課前預(yù)習(xí)和課后及時(shí)復(fù)習(xí).Wonderfulworld：GardenofEdenDiversityandUnity.Amazing?!..

DefinitionofBiochemistryBiochemistryisthechemistryoflife.

Thestudyofthemolecularbasisoflifeandtheinteractwitheachotherorunderstandinglifephenomenainchemicalterms.Thecombinationofbiologyandchemistryortheapplicationofchemicalprinciplestounderstandbiology..TheChemicalUnityofDiverseLivesLivingorganismsvs.inanimateobjectschemicalcomplexityandorganizationuseenergyinasystemicwayself-replicationandself-assemblyBiochemistryExplains:DiverselivesinunifyingchemicaltermsAllmacromoleculesaremadeofafewsimplecompounds.Musicinourbody!.MainQuestionsforBiochemistryI(thissemester):Whatarethecompositionandstructureofbio-molecules?Howdothesebio-moleculesactandinteractinlivingorganisms？.Allchemicalprocessassociatedwithorganismsatthemolecularlevel-isolatemoleculesanddeterminetheirstructure-analyzetheirfunctionExample:thestudyofDNA

HowlifebeganandevolvedOrganisms:uniformatthemolecularlevel

indicate:theyarosefromacommonancestor

Themainobjectivesaretounderstand.1.ProteinStructureandFunction**

（蛋白質(zhì)的結(jié)構(gòu)和功能）2.

Enzymes:BasicConceptsandKinetics (酶的基本概念及酶促動(dòng)力學(xué))3.Enzymes:Catalytic&RegulatoryStrategies （酶催化和調(diào)控的策略）4.Carbohydrates（碳水化合物）**5.RNA,DNA,andflowofgeneticinformation** (DNA,RNA及遺傳信息的傳遞)Contentsforthissemester:.6.

LipidsandCellMembranes（脂質(zhì)和細(xì)胞膜）Bio-Signaling(生物信號(hào)通路）（Lehninger

和Biochemistry第1-13章）8.

RespondingtoEnvironmentalChanges Thesensorysystems&TheImmunesystem

Biochemistry:Chpt.32&33Contentsforthissemester（續(xù)）:.PartIITransducingandStoringEnergy

（能量的轉(zhuǎn)換和貯存）PartIIISynthesizingtheMoleculesofLife

（生物分子的合成）Nextsemester:BiochemistryIITopresentdialogues,actions,stories,anddramawithBiochemicals

.TheAimsofthisCoursesIntroducethelanguageofbiochemistry： --meaning,origin,&significanceofterms2.Understandthephysical,chemical&biologicalcontextofbio-molecule,reaction&pathways3.ThemostimportanttechniquesorExp.forourunderstandingofbiochemistry.BiochemistryAgricultureMolecularBiologyMolecularGeneticsMicrobiologyImmunologyMedicine&Pharmacy(藥)ClinicalMedicine臨床醫(yī)學(xué)

PreventiveMedicinePathology病理

Pharmacology藥理

ApplicationofBiochemistry.BiochemistryandBiotechindustryCellandGeneengineeringPharmaceuticalindustry,proteindrugs,vaccineEnzymeandFermentationengineeringBiochemistryandAgriculturebetterherbicidesandpesticidesgeneticallyengineeredplants.BiochemistryandMedicine

Diagnosis Biochemicalchanges:enzymes,sugaretc ImmunologicalMethods Genediagnosis:chips(Gene&Proteinchips)Therapy Chemotherapy (mostmedicinecurethediseasesbyselectivemodulatehostbiochemicalmetabolite) Genetherapyofcancer,AIDS,geneticdisease.StageI1870s’~1930s’--ChemicalConstitutionofLivingOrganismsStageII1930s’~1950s’--LawofChemicalChangeandControlofDifferentBio-moleculesStageIII1950s’~present--PrinciplesthatareCentralforUnderstandingLivingOrganisms.TheDevelopmentofBiochemistry.ABriefHistoryofBiochemistryoverthelast200years(milestones)1810–30:C,H,O,andNarethemajorsubstancesfromanimalsandplants.Theterm“Protein”wasfirstusedin1838.1850–90:Carbohydrates,lipids,andnucleicacidswererecognized.Theterm“biochemistry”wasformedin1877byHoppe-Seyler.1890s:Yeastextractfermentsugartoalcohol!Enzymescanfunctionincell-freesystem.Theeraofenzymologydeveloped(1894)..1920sJamesSumner:Enzymesareproteins.1940s-1950sAveryandHershey:DNAcarriesthegeneticinformation.1950sFranklin,andWatsonandCrick: DNAisadoublehelix.1960sNirenberg:Geneticcodesdeciphered.1980sCech:RNAhascatalyticactivity (Ribosome)..Pauling thenatureofchemicalbond; thestructureofproteinsand othermacromolecules; theoriesaboutmolecular disease,suchassickle-cell anemia.SomeofNobelLaureatesinthehistoricaldevelopmentofBiochemistry.Krebs:CitricAcidCycle(TCA):animportantwaybywhichthecomplexchemicalprocessesprovidelivingorganismswithhighenergyphosphate.Sanger:SequencingMethodAminoacidsequencingmethodandthecompletesequenceofinsulin.SangerSequencingMethodforDNA.(OswaldAvery,ColinMacleodandMaclynMcCarry)(有莢膜,S;致病性）Avery:DNAcarriesgeneticmaterial.（無(wú)莢膜,R；非致病性）.S(heat-killed)Mouselives毒力株經(jīng)加熱滅活后會(huì)失去其致病性.R+S(heat-killed/extracts)Mousedies.結(jié)果小結(jié)和分析

（背景：以往認(rèn)為蛋白質(zhì)攜帶遺傳信息）有莢膜的活細(xì)菌（S）： 具致病性；無(wú)莢膜的活細(xì)菌（R）： 無(wú)致病性S

菌株加熱滅活后： 無(wú)致病性滅活后的S菌株＋活細(xì)菌R：具致病性！提示 S菌株中的遺傳信息被導(dǎo)入活細(xì)菌R 該遺傳信息對(duì)熱不敏感，不是蛋白質(zhì)

未知的物質(zhì)攜帶了遺傳信息?。?DNAcarriesthegeneticinformation.1869,Miescherisolatesnuclei1944,AverydiscoversthatDNAcarriesthegeneticmaterial1953,WatsonandCrickproposethedouble-helicalstructureofDNAVariousprocessconcernedwithDNA.ex.semi-conservativereplication..DNA,RNAandProteinsynthesisS.Ochoa&A.Kornberg:EnzymaticsynthesisofRNAandDNA(1959).M.W.Nirenberg&H.G.Khorana:Thegeneticcodesinproteinsynthesis(1968).F.Jacob,A.Lwoff,&J.Monod：Mechanismstoswitchon/offgenescells(1965)D.Baltimore,R.Dulbecco,H.M.Temin：Reversetranscriptase

(1975).B.

McClintock:mobilegeneticelements(1983).S.Tonegawa:geneticprincipleforthegeneration ofantibodydiversity(1987).S.Altman&T.R.Cech:RNAcatalyzeRNAprocessing(Ribozyme，1989)R.J.Roberts&P.A.Sharp:eukaryoticgenesare splitandsplicedaftertranscription(1993)M.Rodbell:GTP-bindingproteins(1994).GunterBlobel,intrinsicsignalsgovernprotein localization(1999)..吳憲：與美國(guó)哈佛醫(yī)學(xué)院Folin一起首次用比色定量方法測(cè)定血糖?；貒?guó)后與其他科學(xué)家在蛋白質(zhì)變性理論，血液生化，免疫化學(xué)，內(nèi)分泌學(xué)等多方面研究作出貢獻(xiàn)。上海生化所王應(yīng)睞等于1965年人工合成具有生物活性的牛胰島素；1983年完成酵母AlatRNA的人工全合成。AchievementsofChineseBiochemists.ModernBiochemicalScience

commonlanguageofbiology:概念和方法Define

chemicalmechanismsincriticalprocess oflife.

RevealethechemicalunityindiversityoflivesLivingorganisms(e.g.,E.coli&human)aresimilaratthemicroscopicandchemicallevel.ThebuildingblocksformacromoleculesaresameTheflowofgeneticinformationisthesame(fromDNAtoRNAtoprotein)..greatimpactonmedicine&agriculture Causeofdisease,diagnosisandtreatment Rationaldesignofnewdrugs Generationofcropsanddomesticanimals withnew(geneticmodified)featuresCreatenewconcepts&techniquestodealwith theprimaryquestionsinbiology/medicine Mechanismofcelldifferentiation， development，Carcinogenesis Molecularbasisofmemory,thinking…etc.HowtoStudyBiochemistryExamine：Criticalexp.

formajordiscoveriesUnderstand:

Majorthemesinbiochemistry,e.g.,thepropertiesandfunctionsofnon-covalentinteractions,allostericregulation,etc.Getasenseofdevelopingandevolvingconceptsandknowledge.Whatwearelearningtodaymaybemodifiedorcorrectedtomorrow.PartIFoundationsofBiochemistry1.Themolecularlogicoflife2.Bio-molecules3.

Cells4.WaterSomeImportantChemicalConceptsandPrinciplesforStudyingBiochemistry.GeneralFeaturesofLivingOrganismcomplicated&highlyorganizedstructuresmetabolize--usenutrientsandenergyfrom theirenvironmentrespond(adapt/survive)toitssurrounding tofindenergyandrawmaterialsselfreplicateandselfassemblyevolveanddiversifyThemolecularlogicoflife.

ChemicalUnityofDiverseLivingOrganisms

(生命體化學(xué)組成上的一致性和多樣性)★Composedoflifelessmolecules★Thesemoleculesconformtophysicalandchemicallawswhenexaminedindividually★L(fēng)ivingorganismsmaintainhighlyorderedstatesbyconsuminginanimatematerialsfromenvironment.Alllivingorganismsbuildmoleculesfromthesamekindsofmonomericsubunits..Thestructureofamacromoleculedeterminesitsspecificbiologicalfunction.Eachgenusandspeciesisdefinedbyitsdistinctivesetofmacromolecules.MoleculescontainedinorganismsWater(50-95%)Ions(1%)Organicmolecules(Rest)Livingmatteriscomposedmostlyofthesixlighterelements:

C,H,O,N,P,SH,O,N,andC:thelightestelements(lightestelementsformthestrongestbonds)Bio-molecules.Thetraceelements(Fe,Cu,Mn,Zn,I,Mg)areabsolutelyessentialtolife..Bio-molecules:CompoundsofCarbonCarbon:至少占細(xì)胞干重的一半WhyCarbon?versatilebondingcapacityEachCatomcanformverystablesinglebondwith1-4otherCatoms;anddoubleortriplebondsbetweentwoCatoms.CovalentlylinkedCatomscanformdifferentstructures（linear,branched,orcyclic）addingfunctionalgroupsconferringspecificactivitiestothemolecules..Versatilityofcarboninformingcovalentbonds.Organiccompounds:Moleculescontainingcovalentlybondingcarbonbackbones;e.g.alcohols,amines,aldehydes(醛),ketones,羧基,巰基,…etcMostbio-moleculesareorganiccompounds.

“C”:tetrahedralarrangementofitsfoursinglebonds.C-Csinglebondshavefreedomofrotation,butnotdoublenortriplebonds.Nootherchemicalelementhasthecapacitytoformmoleculesofsuchwidelydifferentsizes,shapes,withvarietyoffunctionalgroups..★Mostbiomoleculescanbeconsideredtobederivedfromhydrocarbons★hydrophilicinteractionsbetweenbiomoleculesHydrocarbons.fisherBall-and-stickSpacefillingBio-moleculeshave3-Dstructures.Bio-moleculeshave3-DstructuresThespecialfeatureoforganiccompoundsisNOTtheircompositionsbutthewaytheiratomsarecombined(structures,

1820s)Corollary:twosubstancesmayshowthesamechemicalformulabutphysicallyandchemicallydifferentmaterials(differentstructuresandfunctions)..Conventionusedforconfiguration.Lightabsorbingpigmentinrhodopsinanintegralmembraneprotein.Chiral：手性..Interactionsbetweenbio-moleculesarestereo-specificBetweenpairsofenantiomers對(duì)映(結(jié)構(gòu))體： usuallyonlyoneformisbiologicallyactive. L-aminoacids(S)arefoundinproteins D-glucose(R)isbiologicallyactiveOnlyonechiralformisgeneratedinlivingcellsduetoenzymespecificity(1975NobelPrize)

Incontrast:thetwoenantiomersareusuallysynthesizedinequalamountsinvitrochemicalsynthesis.Conventionfromorganicchemistry.Chewinggums綠薄荷香菜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－還原反應(yīng))Internalre-arrangements(isomerization,異構(gòu))Cleavage&formationof“C-C”bondsGrouptransfer(親核取代)CondensationBiochemicalReactionSimilartootherchemicalreactions--

brokenandformationofcovalentbonds.Oxidation：gainsoxygenorloseshydrogenReduction：losesoxygenorgainshydrogenOxidation-ReductionReactions.theintra－molecularshiftofatoms/groups

Internalre-arrangements(isomerization,異構(gòu))

.Energy：thecentralthemeinBiochemistry

LivingcellsneedaconstantflowofenergytopreventthemfrombecomingdisorderedLivingcellshaveevolvedsubtlemechanismsforgeneratingandusingenergy.AlllifeprocessesconsistofchemicalreactionscatalyzedbyenzymesThereactionsinalivingorganismareknowncollectivelyasmetabolism(代謝）AcquisitionandutilizationofenergySynthesisofmolecules：forcellstructureandfunctioningRemovalofwasteproductsBiochemicalReactioninlife.DefinitionofMetabolismThehighlyintegratednetworkofchemicaltransformations.Degradation(decreasingorder,thusenergyreleasing)toprovideenergy,catabolism;Synthesis(increasingorder,thusenergyconsuming)toprovidebuildingmaterials,anabolism..TheRolesofmetabolismExtractenergyandreducingpowerfromtheenvironment(生命體通過(guò)光合作用和氧化作用從外界吸收能并釋放廢棄物）Generation(interconversion)ofallthebiomoleculesforalivingorganism(biosynthesis).（伴隨著物質(zhì)和能量代謝，生物分子間通過(guò)分解和合成作用發(fā)生互換）.Anabolism合成代謝Catabolism

分解代謝能源物質(zhì)中間代謝產(chǎn)物廢棄物.GeneralFeaturesofmetabolismlinear,branchedorcircularpathways;Highlyinterconnected

各個(gè)途徑相互交接，形成物與能的網(wǎng)絡(luò)化交流系統(tǒng)

Tightlyregulatedtoachievebesteconomy精密調(diào)控機(jī)制保證機(jī)體最經(jīng)濟(jì)的利用物質(zhì)和能量.Alllivingorganismsaremadeupofcells, thesmallestunitboththestructural andfunctionaloflivingmatters.Cellsarecapableofself-reproduction.Mostcellsaremicroscopicinsize Eukaryoticcells:5-100mminsize； bacteria:1-2mm;mycoplasma:0.3mmCell:FundamentalUnitofLife.Prokaryotic(原核）cells:Lackanucleuse.g.,EubacteriaandarchaeaSimplestructure;Abundant&diverseEukaryotic（真核）cellsPossessanucleusboundedbymembrane,containinggeneticinformationintheformofchromosomesComparison:seeTable2-1,p29LehningerTwocategoryofcells.EukaryotesLargerCellvolume；Morecomplicatedcellstructure,withmembrane-boundednucleusandorganelles(細(xì)胞器）Energymetabolism:

moreunifiedandpackedinmitochondriaWithcytoskeletonandintracellularmovementCelldividedbymitosisFormmulti-cellularorganisms..AdividingE.coli大腸桿菌.Saccharomycescerevisiae(baker’syeast).★Permittheconcentrationofreactantandproductmolecules★Makeintricateregulatorymechanismpossible★Cellsofmulti-cellulareukaryotesareabletorespondquicklyandeffectivelytotheintercellularcommunicationAdvantagesfromOrganelles.AdvantagesofMulti-cellularorganisms

overunicellularones★Possessarelativelymorestable,controlledenvironmentforcells★Cellshaveadivisionoflaborallowinggreatercomplexityinbothformandfunction★Abletoexploitenvironmentalresourcesmoreeffectively★Theyarehighlyorderedlivingsystems.NucleusStorethegeneticinformationcarrier(DNA)SurroundedbyanNenvelop(doublemembraneswithspecializedpores).TheouterlayeriscontinuouswithERmembranesystem.DNAiscondensed螺旋(compressedabout10millionfoldinthelineardimension)inahumanchromosome染色體..Nuclearporesnucleolus.DNA被螺旋壓縮(10millionfold

inthelineardimension)后組成染色體..EndoplasmicReticulum(ER)內(nèi)質(zhì)網(wǎng)acontinuousmembranesystemconsistoftubes&flattenedsacsforminganenclosedlumen

Ribosomes(synthesizeproteins)areattachedtothecytoplasmicsurfaceofER,formingtheroughER(RER)structure.

SmoothER(oftentubular)：thesiteforlipidsynthesis；generatestransportvesicles

thatfusewithothermembranesystemsinthecell...GolgiApparatus:processandsortproteinsastackofflattenedmembranesacssurroundedbymanysmallvesicles.structurallyandfunctionallyasymmetric,thecissidefaceER；transfaceplasmamembraneProteinsandlipidsmovethroughGolgi

體,enteringfromthecissideandexitingfromthetransside.Duringthisprocess,theyareextensivelymodified,e.g.,glycosylated

糖基化,sulfated硫酸化,phosphorylated

磷酸化,etc..Mitochondria線(xiàn)粒體

Withasmoothoutermembraneandaninfoldedinnermembrane(formingmanycrista

突起).Hundredsofenzymescatalyzingtheenergywerecontainedwithininnermembrae,andgeneratetheenergycarrier(ATP)ContainsitsownDNA,RNA,ribosomes

核糖體!Itduplicatesitselfwhencelldivides.Playimportantroleincellapoptosis(凋亡）.Lysosomes溶酶體.M吞噬處理入侵細(xì)菌及提呈抗原的機(jī)制.PlasmamembranePerformsseveralvitalfunctionsforthecell:Transport,whichrequirescarrierandchannelproteinsProvidesmechanicalstrengthandshapetothecellCellcommunicate,responsetoextracellularsignals;specializedfunctionssuchasmusclecontractionandnerveimpulseconduction.Plasmamembraneisalipidbilayercomposedoflipidandproteinmolecules.Others：Peroxisomes過(guò)氧化物酶體Chloroplasts葉綠體Thecytoskeletonsystem……etc.Aroughanalogybetweenthethecellandthehumansociety

Nucleus:thehighestadministrativesection.Mitochondriaandchloroplasts:thepowerplant.

GolgiApparatus:thepostofficeCytoskeletonsystem:thehighways(transportation)

Lysosomes:therecyclingcenterER:thefactory，training&educationcenterPlasmamembrane:theborderlineLikethesociety,thecytoplasmiscrowded,highlyorganized,anddynamic..2004年世界十大科技進(jìn)展新聞是：

1.“勇氣”&“機(jī)遇”號(hào)發(fā)現(xiàn)火星有水的證據(jù)..ItisNOTanaccidentthatlifearoseinassociationwithwater,sincethissubstancehasseveralunusualpropertiesthatsuitstobethemediumoflifeThermalpropertiesSolventcharacteristicsWater:MediumofLife.

ThermalProperties:

Water’smelting&boilingpointsareexceptionallyhighcomparedwithrelatedmoleculesofsimilarmolecularweight..Water’shighheato