Chapter3

EnzymesChapter31Enzymesarebiocatalystswithhighspecificityandhighlycatalyticefficencyproducedbylivingcells.Besidesproteins,ribozymesanddeoxyribozymesarealsoenzymes.Whatisenzyme?Enzymesarebiocatalys2（1）producingsite:livingcells（2）property:most——proteinsafew——RNADNA（3）function:biochemicalcatalyzation（1）producingsite:living33.1StructureandFunctionofEnzymes3.2PropertiesandCatalyticMechanismsofEnzymes3.3KineticsofEnzyme-CatalyzedReactions3.4RegulationofEnzymeActivity3.5NomenclatureandClassificationofEnzymes3.6ClinicalApplicationsofEnzymes

OUTLINE3.1StructureandFunctionof43.1StructureandFunctionofEnzymes3.1StructureandFunctionof53.1.1structureofenzymesenzymesSimpleenzymes——proteinsapoenzymeprostheticgroupcoenzymeConjugatedenzymes(holoenzyme)cofactorcompositionofEnzymeMoleculesHoloenzyme=Apoenzyme+Cofactors3.1.1structureofenzymesenzy6Prostheticgroup:

tightlybondwithapoenzymeandcannotberemovedbydialysis（分離，透析）orultrafiltration.FAD,metal,etc.Coenzyme:

looselybondwithapoenzymeandcanberemovedbydialysisorultrafiltration.NAD,NADP,etc.Cofactorsaresmallorganic（有機(jī)的）moleculesorinorganic（無機(jī)的）ionsrequiredforenzymeactivities.Prostheticgroup:Cofactorsar7coenzymesmallorganicmoleculesmetalionIron,magnesium,cobalt,manganesecoenzymesmallorganicmolecule8Functionsofsmallorganicmolecules：actascarrierstotransferelectrons,protons（質(zhì)子）orothergroups.Functionsofsmallorganicmol9CoenzymesTransferredgroupsVitaminsNicotinamideadeninedinucleotide(NAD+)H+,eV-ppNicotinamideadeninedinucleotidephosphate(NADP+)H+,eV-ppFlavinadeninedinucleotide(FAD)H V-B2Flavinmononucleotide(FMN)HV-B2Thiaminepyrophosphate(TPP)-CHO(aldehyde)V-B1CoenzymeA(CoA)R-CO-(acyl)PantothenicacidPyridoxalphosphate-NH2V-B6BiotinCO2BiotinTetrahydrofolate“C”(onecarbonunit)Folicacid5-deoxyadenosylcobalamineCH3、-CnH2n+1(alkyl)V-B12TABLE3-1CofactorsofenzymesCoenzymesTransferredgroupsVit10coenzymesmallorganicmoleculesmetalionIron,magnesium,cobalt,manganese(Fe)(Mg)(Co)(Mn)coenzymesmallorganicmolecule11metalloenzymebindmetaliontightlymetalionisretainedthroughoutpurificationmetal-activatedenzymebindmetalionlesstightlymetalionisessentialforactivitymetalloenzyme12Functionsofmetalion：stabilizeenzymeconformationparticipateinreactionbytransferringelectronsapproximationandorientationofreactantsasbridgebetweensubstrateandenzymeneutralizenegativechargestodecreaseelectrostaticrepulsionFunctionsofmetalion：13

monomericenzyme：onlycontainapolypeptidechainwithtertiarystructure.

oligomericenzyme：containtwoormorepolypeptidechainsassociatedbynoncovalentbonds.monomericenzymes,oligomericenzymesandmultienzymecomplexmonomericenzyme：onlycontain14multienzymecomplex：differentenzymescatalyzesequentialreactionsinthesamepathwayareboundtogether.multienzymecomplex：different15compositionofpyruvatedehydrogenasecomplexEnzymescofactorsPyruvatedehydrogenaseTPPDihydrolipoyltransacetylaselipoicacid&.CoADihydrolipoyldehydrogenaseFAD&.NAD+Pyruvate+CoA+NAD+

acetylCoA+CO2+NADH+H+Pyruvatedehydrogenasecomplexcompositionofpyruvatedehydr16multifunctionalenzyme（tandemenzyme）：asinglepolypeptidechainwithmultipleactivities.multifunctionalenzyme（tandem17FattyacidsynthesismultifunctionalenzymeofmammalThisenzymeconsistsofsevenenzymeactivitiesinasinglepolypeptidechainencodedbyagene.FattyacidsynthaseFattyacidsynthesismultifunc183.1.2.ActivesiteofanenzymeEssentialgroups：Somechemicalgroupsessentialformaintainingtheenzymeactivityaretermedessentialgroups.Primarystructureandspatialstructureofchymotrypsin3.1.2.Activesiteofanenzym19Activesite:

Theactivesiteistheregionoftheenzymethatcontainssomechemicalgroupsforbindingsubstratesandtransformingitintoproducts.Theactivesiteisathree-dimensionalentity,oftenacleftorcreviceonthesurfaceoftheprotein,inwhichthesubstrateisboundbymultipleweakinteractions.Activesite:Theactive20Three-dimensionalstructure

SubstratebindingThree-dimensionalstructureSu21substrateEssentialgroupsoutsideofactivesite

Bindinggroupscatalyticgroup

activesiteActivesiteofenzymes

substrateEssentialgroupsout22Essentialgroupsactivesiteoutsideofactivesite：

maintainconformationofenzymeSubstrate-bindinggroupscatalyticgroupdeterminespecificityforsubstratedeterminecharacteristicsofcatalyzationEssentialgroupsactivesiteout233.1.3IsoenzymesIsoenzymes:Multipleformsofanenzymewhichcatalyzethesamereaction,butdifferfromeachotherintheiraminoacidsequence,physicochemicalpropertiesandimmuno-characters.3.1.3IsoenzymesIsoenzymes:24Lactatedehydrogenase(LDH)

HsubunitMsubunitTetramerLDH(M.W.130,000)Subunit:H(Chr12)

M(Chr11)pyruvateLactateLDHLactatedehydrogenase(LDH)H25originLDH5LDH4LDH3LDH2LDH1CelluloseAcetateMembraneElectrophoresisresultofLDHisoenzymes_+anodecathodeH4M4H1M3H2M2H3M1originLDH5LDH4LDH326TissuedistributionspecificityLDH1(H4)LDH2(H3M)LDH3(H2M2)LDH4(HM3)LDH5(M4)Tissuedistributionspecificit27Physiologicalsignificanceofisoenzymesregulationofmetabolism(differenttissueordifferentdevelopmentalstage).diagnosisofdifferentdiseases.EnzymeactivityinfarctionNormalLiverDiseaseLDHisoenzymograminserumPhysiologicalsignificanceof283.2PropertiesandCatalyticMechanismsofEnzymes3.2PropertiesandCatalyticM29Theessentialpropertiesofbothenzymesandinorganiccatalysts:

Onlycatalyzethermodynamicreactions.Remainunchangedoftheirqualityandquantity.Increasetherateofreaction,butcannotaltertheequilibriumconstantofthereaction.Decreasetheactivationenergyofreactiontoincreasethevelocityofthereaction3.2.1PropertiesofenzymecatalyzedreactionsTheessentialpropertiesofbo30HighlyCatalyticActivityofEnzymesIngeneral,enzyme-catalyzedreactionsare108~1020timesfasterthanthecorrespondinguncatalyzedreactions，107~1013timesfasterthaninorganiccatalyticreactions.Thetemperatureneededisnothigh.Enzymesdecreasetheactivationenergymoreeffectivelythaninorganiccatalysts.

propertiesofenzymesthataredifferentfrominorganiccatalysts:HighlyCatalyticActiv31example:2H2O22H2O+O2

catalystsefficiency

Fe2+610-4mol/g.Sheme610-1mol/mol.Speroxydase6106mol/mol.Sexample:2H2O232Specificity：

Specificityreferstotheabilityofanenzymetodiscriminatebetweentwocompetingsubstrateandcatalyzeonespecificreaction.

HighlySpecificityofEnzymes

Specificity：HighlySp33

Absolutespecificity:

Anenzymejustactsonaspecialsubstrate.Forexample,ureaseonlyhydrolyzesureatoformNH3andCO2.

Relativespecificity:

Anenzymeactsonagroupofrelatedsubstratesoronetypesofchemicalbond.Forexample,peptidaseandhexokinase,etc.

Stereospecificity:

Anenzymeactsonasinglestereoisomer.Forexample,LDHhydrolyzesL-lactate.Absolutespecificity:Anenz34CompartmentationIsoenzymesAllostericregulation(3.4)Covalentmodification(3.4)Inductionandrepression(3.4)ActivitiesofenzymescanberegulatedCompartmentationActivi353.2.2.CatalyticMechanismsofenzymesEnzymesacceleratereactionsbydecreasingtheactivationenergy.3.2.2.CatalyticMechanismsof36Forabiochemicalreactiontoproceed,theenergybarrierneededtotransformthesubstratemoleculesintothetransitionstatehastoovercome.Thetransitionstatehasthehighestfreeenergyintheenergypathway.FormationofEnzyme-substrateComplexandInduced-fitHypothesisThecombinationofsubstrateandenzymeforcesthesubstratetobecomethetransitionstate.Forabiochemicalr37activationenergy：thefreeenergyrequiredtopromotereactantsfromthegroundstatetothetransitionstateinchemicalreactions.activationenergy：thefreeene38Energydiagramforcatalyzedanduncatalyzedreactions．Energydiagramforcatalyzeda39Enzyme-substratecomplexEnzyme-substratecomplex40

Howdoesanenzymelowertheactivationenergyofareaction?Formationoftheenzyme-substratecomplex(ES)

E+SESE+PTransitionstateHowdoesanenzymelowerthe41model----

enzymebinditssubstrateInducedfitmodelhypothesis

DanielE.Koshland,1958HowdoestheESform?model----

en42InducedfitmodelInducedfitmodel43InducedfitmodelActivesitesintheuninducedenzymeBindingofthefirstsubstrate(gold)inducesaconformationalshiftthatfacilitatesbindingofthesecondsubstrate(blue),withfarlowerenergythanotherwiserequired.Whencatalysisiscomplete,theproduct

isreleased,andtheenzymereturnstoitsuninducedstate.

InducedfitmodelActivesites44Hexokinase-D-glucosecomplexHexokinaseInducedfitHexokinase-D-glucosecomplexHe45Induced-fitmodelofcarboxypeptidasesubstrateInduced-fitmodelofcarboxype46(1)Proximityandorientationeffects

Catalyticmechanismsofenzymes(1)Proximityandorientation47FIGURE3-7ProximityeffectsandorientationarrangeFIGURE3-7Proximityeffectsa48(2)Electrostaticeffects

Theactivesitesofenzymesareoftenhydrophobic.Waterislargedlyexcludedfromtheactivesitebecauseofthelowdielectricconstant.Thisincreasestheelectrostaticinteractionsbetweenenzymesandsubstratesandacceleratevelocityofthereaction.(2)Electrostaticeffects49(3)Acid-basecatalysis

Sidechaingroupsinenzymeactivesites,actasprotondonorsoracceptorsaretermedgeneralacidsorgeneralbases.Thetransitionstateisstabilizedandtherateofreactionisincreasedbyaddingorremovingprotonfromreactants.Thesechemicalgroupsareimidazolegroup,aminogroup,carboxylgroup,andsoon.(3)Acid-basecatalysis50(4)Covalentcatalysis

Theattackofnucleophilicorelectrophilicgroupintheenzymeactivesiteuponthesubstrateresultsincovalentbindingofsubstratetotheenzymeasanintermediateinthecauseofcatalysis.Ser-OH—CH2—S··：H—CH2—O··：HCys-SH—CH2—C=CHHNNCH：His-imidazolenucleophilic(4)Covalentcatalysis513.3KineticsofEnzyme-catalyzedReactions3.3KineticsofEnzyme-catalyz52KineticsofEnzyme-CatalyzedReactions:isastudyontherateofenzyme-catalyzedreactionsandthefactorsaffectedthereactionrate.Thefactorsaffectedtherateofenzyme-catalyzedreactions：substrateenzymetemperaturepHactivatorinhibitorKineticsofEnzyme-CatalyzedR53Thevelocityofabiochemicalreactionisdefinedasthechangeintheconcentrationofasubstrateorproductperunittime.Thevelocityofabioch54

Theinitialvelocity（初速率,V0)

isthereactivevelocityduringthefirstfewsecondsofthereaction,andisdeterminedastheslopeofthecurvethroughthelinearphaseintheplotofproductconcentrationsversusreactivetimeTheinitialvelocity（初速55Enzymeactivitymaybeexpressedinanumberofways,thecommonestisbytheV0.Thereare2standardunitsofenzymeactivity:

Internationalunit(IU)andthekatal(kat)1IU：theamountofenzymethatproduce1μmolofproductperminat25oCunderoptimalconditions.1kat:theamountofenzymethatconverts1molofsubstratetoproductpersecondat25oCunderoptimalconditions.

1IU=16.67x10-9katEnzymeactivitymaybeexpress56Specificactivityisthenumberofunitspermilligramofprotein(units/mg).Thespecificactivityisameasureofthepurityofanenzyme.Specificactivityisthenumbe573.3.1.Theeffectofsubstrateontherateofenzyme-catalyzedreactionsPreconditions:Initialvelocity(V0)[S]ismuchgreaterthan[E]Rectangularhyperbolaplot3.3.1.Theeffectofsubstrate58Firstorderreaction:

Therateofthereactionisdirectlyproportionalto[S]onlywhen[S]islow.Firstorderreaction:59Zero-orderreaction:

When[S]issufficientlyhigh,thevelocityapproachmaximumvelocity(Vmax).Zero-orderreaction:60Mixed-orderreactionMixed-orderreaction61K1=rateconstantforESformationK2=rateconstantforESdissociationK3=rateconstantforproductformationandreleasefromtheactivesite

Enzyme-catalyzedreactionprocessK1=rateconstantforESforma62Km：MichaelisconstantMichaelis-MentenEquation(1913)

K2+K3Km=K1

Km：MichaelisconstantMichaeli63[S]K[S]VVmm+=V=VmKm[S]FirstorderMixed-orderZero-orderV≌Vm當(dāng)[S]>>Km時(shí),當(dāng)[S]<<Km時(shí),V=VmKm[S][S]K[S]VVmm+=V=VmKm[S]Firsto6ThesignificanceofKmandVmaxV=Vm[S]Km+[S]WhenV=Vm2Km=[S]KmisequaltothesubstrateconcentrationatwhichthereactionrateishalfofitsVmax.Kmischaracteristicconstantofanenzyme-catalyzedreaction.Kmhasunitsofmolarity.KmindicatestheaffinityofEandS.ThesignificanceofKm65EnzymesSubstratesKmvalues(mmol/L)Hexokinase(brain)ATPD-glucoseD-fructose0.40.051.5β-GalactosidaseD-lactose4.0ThreoninedehydrataseL-Threonine5.0CarbonicanhydraseHCO-3

9.0ChymotrypsinN-benzoltyrosinamideGlycyltyrosylglycine2.5108TABLE3-2Km

valuesforsomeenzymesEnzymesSubstratesKmvalues(66ThesignificanceofKmandVmaxVmaxisthevelocitywhenallenzymemoleculesaresaturatedwithsubstrates.Vmax=k3[E]TThesignificanceofKmandVma67Turnovernumber:thenumberofsubstratemoleculesconvertedintoproductbyanenzymemoleculeinaunitoftimewhentheenzymeissaturatedwithsubstrate.Itcanbeusedtocomparecatalyticactivityofenzymes.Turnovernumber:thenumberof6MeasurementofKmandVmaxMichaelis-MentenRectangular-hyperbolicplot

MeasurementofKmand69Lineweaver-BurkDouble-reciprocalplot

y=mx+bSlope=km/Vmax(interceptontheverticalaxis)

(interceptonthehorizontalaxis)

Lineweaver-BurkDouble-recip703.3.2.Theeffectofenzymeconcentrationontherateofenzyme-catalyzedreactions[S]>>[E]時(shí),V=k3[E]V[E]03.3.2.Theeffectofenzymeco713.3.3.Theeffectoftemperatureontherateofenzyme-catalyzedreactionsEnzymeactivityTemperature(°C)optimumtemperatureOptimumtemperature:

Temperatureatwhichitoperatesatmaximalefficiency.Itisnotacharacteristicconstantofanenzyme.

Bell-shapedcurve3.3.3.Theeffectoftemperatu723.3.4.TheeffectofpHontherateofenzyme-catalyzedreactionsOptimumpH:

ThepHvalueatwhichanenzyme’sactivityismaximal.Itisnotacharacteristicconstantofanenzyme.PepsinAmylaseEnzymeactivitypHAcetylcholinesterase3.3.4.TheeffectofpHonthe733.3.5Theeffectofinhibitorsontherateofenzyme-catalyzedreactionsInhibitor:

anymoleculewhichactsdirectlyonanenzymetoloweritscatalyticratewithoutdenaturation.irreversibleinhibitionreversibleinhibitioncompetitiveinhibitionnon-competitiveinhibitionuncompetitiveinhibitionClassificationofinhibitions3.3.5Theeffectofinhibitor7IrreversibleenzymeinhibitionIrreversibleinhibitorsusuallybondcovalentlytotheenzyme,oftentoasidechaingroupintheactivesite.Inhibitioncannotbereversedbydialysisorultrafiltration.Irreversibleenzymei75Example1

organophosphorouscompoundsRegenerationofactiveenzyme——pyridinealdoximemethyliodide(PAM)Example1organophosphorous76Example2

compoundswithheavymetalions(Hg2+、Ag+、As3+ect.)-SHenzymelewisiteInhibitedenzymeRegenerationofactiveenzyme——2,3-dimercaptopropanol(BAL)BALInhibitedenzymeCompondwithAsactiveenzymeExample2compoundswithhea77Example3

AntibioticpenicillinExample3Antibioticpenicil7reversibleenzymeinhibitionReversibleinhibitorcandissociatefromtheenzymebecauseitbindsthroughnoncovalentbonds.Ipetitiveinhibitionnon-competitiveinhibitionuncompetitiveinhibitionformsreversibleenzymeinh791)CompetitiveinhibitionAcompetitiveinhibitortypicallyhasclosestructuralsimilaritiestothenormalsubstratefortheenzyme.Itcompeteswiththesubstratemoleculesforbindingtotheactivesiteoftheenzyme.1)Competitiveinhibition80CompetitiveinhibitionAthighsubstrateconcentration,theeffectofacompetitiveinhibitorcanbeovercome.Competitiveinhibition81Competitiveinhibitioninhibitor

NoinhibitorLineweaver-BuckplotKmincreasedVmaxunchanged

NoinhibitorinhibitorvCompetitiveinhibitioninhibit82ExampleofcompetitiveinhibitionExampleofcompetitiveinhibit83ClinicalapplicationofcompetitiveinhibitionClinicalapplicationofcompet84(2)Noncompetitiveinhibition

Anoncompetitiveinhibitorbindsatasiteotherthantheactivesiteoftheenzymeanddecreasesitscatalyticratebycausingaconformationalchangeinthethree-dimensionalshapeoftheenzyme.(2)Noncompetitiveinhibitio85NoncompetitiveinhibitionTheinhibitorusuallybearslittleornostructuralresemblancetoS.TheESIcomplexdoesnotproceedtoformproduct.Theeffectofanoncompetitiveinhibitorcannotbeovercomeathighsubstrateconcentrations.Noncompetitiveinhibition86Noncompetitiveinhibitioninhibitor

NoinhibitorLineweaver-BuckplotKmunchangedVmaxdecreasedNoncompetitiveinhibitioninhi87(3)UncompetitiveinhibitionUncompetitiveinhibitor

TheinhibitorbindtoEScomplexandresultsindecreaseofbothESandP(alsofreeE).TheESIcomplexcannotbereversedbyincreasing[S].(3)Uncompetitiveinhibition88

noinhibitorinhibitorUncompetitiveinhibitionLineweaver-BuckplotKmdecreasedVmaxdecreasednoinhibitorinhibitorUncompet89InhibitorTypeBindingSiteonEnzymeReactionCompetitiveInhibitorSpecificallyatthecatalyticsite,whereitcompeteswithsubstrateforbindinginadynamicequilibrium-likeprocess.Inhibitionisreversiblebysubstrate.NoncompetitiveInhibitorBindsEorEScomplexotherthanatthecatalyticsite.Substratebindingunaltered,butESIcomplexcannotformproducts.Inhibitioncannotbereversedbysubstrate.UncompetitiveInhibitorBindsonlytoEScomplexesatlocationsotherthanthecatalyticsite.Substratebindingmodifiesenzymestructure,makinginhibitor-bindingsiteavailable.Inhibitioncannotbereversedbysubstrate.InhibitorTypeBindingSiteon90propertiesNoinhibitorsCompetitiveinhibitorsnoncompetitiveinhibitorsuncompetitiveinhibitorsComponentbindingtoIEE、ESESApparentKmKm↑unchanged↓Vmax

Vmaxunchanged↓↓Lineweaver-Burkplot

interceptatxaxis-1/Km↑unchanged↓Interceptatyaxis1/Vmaxunchanged↑↑slopeKm/Vmax↑↑unchangedTable3-3ComparativeeffectsofreversibleinhibitorsonenzymekineticspropertiesNoinhibitorsCompet913.3.6Effectofactivatoronenzymeactivitiesessentialactivator:enablenon-activeenzymetobecomeactiveone.Forexample,Mg2+forhexokinase.non-essentialactivator:enablelow-activeenzymetobecomehigh-activeone.Forexample,Cl-forsalivaryamylase.Activator:

substancesenablenon-activeenzymetobecomeactiveoneorlow-activeenzymetobecomehigh-activeone.

MetalionssuchasMg2+,K+,Mn2+,etc.3.3.6Effectofactivatoron923.4RegulationofEnzymeActivity3.4RegulationofEnzymeActiv93Thethousandsofenzyme-catalyzedchemicalreactionsinlivingcellsareorganizedintoaseriesofbiochemicalormetabolicpathways.Metabolicandotherprocessesarecontrolledbyalteringthequantityorthecatalyticefficiencyofkeyenzymes.keyenzymes:rate-limitingenzymeswiththelowestVmaxThethousandsofenzym94allostericregulationcovalentmodificationzymogenisoenzymesEnzymeactivityregulationEnzymeamountregulationinductionandrepressionenzymedegradationallostericregulationEnzymeac953.4.1.AllostericregulationAllostericregulation:Metabolitesbindstoregionofoutsidetheactivesite,andchangetheconformation,andthustheenzymeactivity.AllostericenzymeAllostericsiteAllostericeffector

AllostericinhibitorAllostericactivator3.4.1.AllostericregulationA96AllostericenzymeAllostericenzymes:areenzymeswhoseactivityatthecatalyticsitemaybemodulatedbyreversible,noncovalentbindingofaspecialmodulatortoaregulatoryorallostericsite.Allostericsite:

isthespecificsiteonthesurfaceofanallostericenzymemoleculetowhichthemodulatororeffectormoleculeisbound.Allostericeffector:isabiomoleculethatbindstoallostericsiteofanallostericenzymeandmodulatesitsactiviry.AllostericenzymeAllostericen97AllostericenzymeAllostericenzymesareoftenmulti-subunitproteinswithanactivesiteoneachsubunit.AllostericenzymeAlloste98生物化學(xué)英文課件-酶99Allostericenzymesoftenhavemorethanoneactivesitewhichco-operatively

bindsubstratemolecules.AllostericregulationThebindingofsubstrateatoneactivesiteinducesaconformationalchangeintheenzymethatalterstheaffinityoftheotheractivesitesforsubstrates.------cooperativityNegativecooperativityPositivecooperativityAllostericenzymesoft100AllostericregulationAplotofV0against[S]foranallostericenzymegivesasigmoidal-shapedcurve.V0[s]AllostericregulationAplotof101AllostericenzymeProteinkinaseA(PKA)InactivePKAcAMPsbindtoallostericsiteofPKAactivecatalyticsubunitsofPKAAllostericenzymeProteinkinas102AllostericenzymeAspartatetranscarbamylase(ATCase)carbamylphosphateN-carbamylaspartateAllostericenzymeAspartatetra103Allostericactivator:ATPAllostericinhibitor:CTPThisenzymeconsistofsixcatalyticsubunitseachwithanactivesiteandsixregulatorysubunitstowhichtheallostericeffectorsCTPandATPbind.AllostericenzymeAspartatetranscarbamylase(ATCase)Allostericactivator:ATP1043.4.2.CovalentmodificationCovalentmodification:

Somegroupsofanenzymecanbindtocertainchemicalgroupsbycovalentbondandchangetheenzymeactivity.typesPhosphorylation&.DephosphorylationMethylation&.DemethylationAcetylation&.deacetylationAdenylation&.deadenylation3.4.2.CovalentmodificationC105PhosphorylationanddephosphorylationThemostcommonmodificationistheadditionandremovalofaphosphategroup:phosphorylationanddephosphorylationrespectively.Phosphorylationiscatalyzedbyproteinkinases,oftenusingATPasthephosphatedonor,teinkinaseproteinphosphatasesPhosphorylationanddephosphor1063.4.3.Zymogen(proenzyme)Zymogen:

Someenzymesaresynthesizedaslargerinactiveprecursorscalledproenzymesorzymogens.Zymogenactivation:Zymogensareactivatedbytheirreversiblehydrolysisofoneormorepeptidebondsundercertainconditions.Theprocessofzymogenactivationisactuallytheprocessofactivesiteformation.3.4.3.Zymogen(proenzyme)Zym107MechanismofzymogenactivationSelectiveproteolysisFormationactivecenteroractivesiteexpositionConformationalchangezymogenDefiniteconditionExamplesincludethehormoneinsulin(proinsulin),pepsinogen,trypsinogen,etc.Mechanismofzymogenactivatio108Trypsinogenactivatedtoformtrypsin

Trypsinogenactivatedtoform109TheprocessofpepsinogenactivationTheprocessofpepsinogenacti110Physiologicalsignificanceofzymogenactivation

Preventautodigestionofthesecretoryorganitself.Forexample,prematureactivationofpancreaticzymogens(trypsinogen,chymotrypsinogenandproelastase)leadstotheconditionofacutepancreatitis

Keeparapidandamplifiedresponsetoconditionchangesbecausezymogensarestorageofenzymes.Physiologicalsignificanceof111（1）synthesisinductionrepression（2）degradation3.5.Regulationofenzymequantity

Cellscansynthesizespecificenzymesinresponsetochangingmetabolicneeds,aprocessreferredtoasenzymeinduction.Thesynthesisofcertainenzymesmayalsobespecificallyinhibited,aprocessreferredtoasenzymerepression.（1）synthesis3.5.Regulationo1123.5NomenclatureandClassificationofEnzymes3.5NomenclatureandClassific1133.5.1.NomenclatureofEnzymeSystematicname

——establishedbyInternationalUnionofBiochemistryandMolecularBiology(IUBMB)Recommendedname3.5.1.NomenclatureofEnzymeS114Serialnumber:EC.X.X.X.X

（EC——EnzymesCommission）Lactate:NAD+oxidoreductaseEC

1.

1.

1.

27Majorclass----oxidoreductaseSubclass----oxidationgroupCHOHSubsubclass----NAD+ashydrogenacceptorNhissubsubclassSystematicname

Substratesarestatedfirst,followedbythereactiontypetowhichtheending-aseisaffixed.Commonname:

Lactatedehydrogenase(LDH)Serialnumber:EC.X.X.X.X