BiochemistryII

--Metabolism:

Thedegradationandsynthesisofbiomolecules.

by

ProfessorZengyiChang(昌增益教授）

Tel:6277-2251

E-mail:changzy@1.AnOverviewofMetabolism

1.1

TheDefinitionofMetabolismThehighlyintegratednetworkofchemicaltransformations.Degradation(decreasingorder,thusenergyreleasing)toprovideenergy,catabolism;Synthesis(increasingorder,thusenergyconsuming)toprovidebuildingmaterials,anabolism.TheenergysupplyanddemandinHeterotrophs:theATP-ADPcycle1.2

TheRolesofmetabolismExtractenergyandreducingpowerfromtheenvironment(photosynthesisandoxidativedegradationofnutrients);Generation(interconversion)ofallthebiomolecules(smallandlarge)foralivingorganism(biosynthesis).1.3TheGeneralFeaturesofmetabolism

Occursinlinear,branchedorcircularpathways;Highlyinterconnected(“EveryroadleadstoRome”).Highlyregulatedtoachievethebesteconomy(“Balancedsupplyanddemand”).Thenumberofreactionsislarge(over1000)andthenumberoftypesofreactionsisrelativelysmall.Wellconservedduringevolution:reflectingtheunityofthelifephenomena(“whathappensinbacteriahappensinhumanbeing”).DegradationisconvergentandenergyreleasingSynthesisisdivergentandenergyconsumingThecitricacidcycle乙酰輔酶A草酰乙酸檸檬酸異戊烯焦磷酸Acetyl-CoA:thecommondegradativeproductofsugar,fattyacidsandmanyaminoacidsCoenzymeA:thecarrierofactivatedacylgroups泛酸巰基乙胺Metabolism:

TheeconomyTheunityTheregulation

2.

Thingsthatwillbecovered

1).Generalprinciplesforbioenergetics.

2).Oxidativedegradationoffuels(glycolysis,b-oxidation,ureacycle,a-ketoacidoxidation, citricacidcycle),generatingNADH,FADH2,ATP,andCO2.

3).OxidationofNADHandFADH2byO2andgenerationofATPandH2O(respiratorychains,ATPsynthase).

4).Photosynthsis(photophosphorylationandcarbonfixation).

5).BiosynthsisofDNA,RNAandProtein(replication,repair,recombination,transcription,translation).

6).Regulationofmetabolism.PreparatoryPhasePayoffPhaseChapter15GlycolysisandcatabolismofhexosesThecitricacidcycleOrtheKrebscycleOrTricarboxylicacidcycleChapter16ThecitricacidcycleChapter17OxidationoffattyacidsChapter18AminoacidoxidationandtheproductionofureaTheureacycleChapter18AminoacidoxidationandtheproductionofureaOxidativePhosphorylation(0ninnermembraneofmitochondria)Chapter19OxidativephosphorylationAndphotophosphorylationChapter19OxidativephosphorylationandphotophosphorylationChapter20CarbohydratebiosynthesisChapter20CarbohydratebiosynthesisTheCalvinCycle(CO2fixation)Chapter21LipidbiosynthesisChapter21Lipidbiosynthesis

Chapter22Biosynthsisofaminoacids,nucleotides,andrelatedmoleculesChapter22Biosynthesisofaminoacids,nucleotides,AndrelatedmoleculesChapter23IntegrationandhormonalRegulationofmammalianmetabolismChapter24GenesandchromosomesProposedwayofcouplingthesynthesisoftheleadingandthelaggingstrandTheloopChapter25DNAmetabolismCleavesattheeighthphosphodiesterbondatthe5’sideofthelesionFourthorfifthphosphodiesterbondatthe3’sideofthelesionProposedmodelfornucleotide-excisionrepairinE.colicellsTheABCexinucleaseChapter25DNAmetabolismThestrandsswitchpositions(byrotatingtherecombinase)

Thetwoyet-cutstrandsarecutatspecificsitesandalsoexchangedcutcutCovalentDNA-recombinaseintermediatesChapter25DNAmetabolismChapter26RNAmetabolismAll64geneticcodesChapter27ProteinmetabolismTheformationofthePeptidebondisprobablycatalyzedbythe23SrRNAribozyme.Chapter27ProteinmetabolismThelactoseoperonintheinduced

state(inthepresenceofaninducer)Chapter28RegulationofgeneexpressionRecombinantDNAcanbegeneratedbyusingrestrictionenzymesandligase.Chapter29RecombinantDNAtechnology3.

UnderstandingMetabolism:aretrospect3.1Sugardegradation(glycolysis)andsynthesis1897,EduardBuchner,Cell-freefermentation(NobelPrizein1907).OttoFritzMeyerhof,conversionofglucosetolacticacidinmuscleandbacktoglucoseinliver(NobelPrizein1922).SirArthurHardenandHansvonEuler-Chelpin,involvementofenzymes,coenzymes,andphosphorylatedintermediates(NobelPrizein1929).CarlFerdinandCoriandGertyTheresaCori,formationofglucose-1-phosphatefromglycogenandpyrophosphatebytheactionofphosphorylase(NobelPrizein1947).LuisF.Leloir,UDP-glucoseistheprecursorforglycogensynthesis(NobelPrizein1970).Thewholeglycolysispathway(conversionofglucosetopyruvate)wasrevealedby1940.3.2Completeoxidationoffuels:fromtwo-carbonunitstoCO2AlbertvonSzent-Gyorgyi,plantacids,fumaricacid(反丁烯二酸),malicacid(蘋果酸)werenotconsumed,butactascatalystsforthecellularcombustionprocess(NobelPrizein1937).FritzAlbertLipmann,roleofco-enzymeAandATP(NobelPrizein1953);SirHansAdolfKrebs,Acetyl-CoAandcitricacidcycle(檸檬酸循環(huán))forcompleteoxidationtwo-carbonunits(NobelPrizein1953).3.3SynthesisofATPusingenergyreleasedfromfueloxidationOttoHeinrichWarburg,involvementofiron-containingcytochromes(細胞色素)incellularrespiration(NobelPrizein1931).PeterD.Mitchell,proposedthechemiosmotictheory（化學滲透學說）torelateelectronflowtoATPsynthesisinallorganisms(NobelPrizein1978).PaulD.Boyer,JohnE.Walker,enzymaticmechanismforATPsynthesis(NobelPrizein1997).Dr.PaulD.BoyerNobelPrizein19973.4LipiddegradationandsynthesisKonradBlochandFeodorLynen,pathwaysforcholesterolandfattyacidsynthesis(NobelPrizein1964).MichaelS.BrownandJosephL.Goldstein,regulationofcholesterolbiosynthesis(NobelPrizein1985).3.5RegulationofMetabolismEarlW.Sutherland,Jr.,cAMPasthesecondmessagerforhormonestoregulatecellmetabolism(NobelPrizein1971).AlfredG.GilmanandMartinRodbell,involvementofmembraneG-proteinsinsignaltransductionofhormones(NobelPrizein1994).EdmondH.FischerandEdwinG.Krebs,regulationofenzymaticactivitybyreversiblephosphorylation(NobelPrizein1992).Dr.EdmondH.FischerNobelPrizein19923.6PhotosynthesisHansFischer,constitutionofchlorophyll(葉綠素)anditssimilaritytoheme(NobelPrizein1930).MelvinCalvin,CalvincycleforCO2assimilation(NobelPrizein1961).JohannDeisenhofer,RobertHuber,andHartmutMichel,3-DstructureofaPhotosyntheticreactioncenterfromapurplebacterium(NobelPrizein1988).3.7DNA,RNAandProteinsynthesisSeveroOchoaandArthurKornberg,enzymaticsynthesisofRNAandDNA(NobelPrizein1959).MarshallW.Nirenberg,HarGobindKhorana,interpretationofthegeneticcodesinproteinsynthesis(NoblePrizein1968).FrancoisJacob,AndreLwoff,andJacquesMonod,Mechanismstoswitchgenesoneandoffinprokaryotes(NobelPrizein1965).DavidBaltimore,RenatoDulbecco,andHowardMartinTemin,enzymaticRNA-dependentDNAsynthesisintumorviruses(NobelPrizein1975).

BarbaraMcClintock,mobilegeneticelementsortransposons(NobelPrizein1983).SusumuTonegawa,geneticprincipleforthegenerationofantibodydiversity(NobelPrizein1987).SidneyAltmanandThomasR.Cech,RNAcatalyzedRNAprocessing(Ribozyme，核酶)(NobelPrizein1989).RichardJ.RobertsandPhilipA.Sharp,eukaryoticgenesaresplitandhavetobespliced(剪接）aftertranscription(Noble