电子教案-糖代谢(英文版)课件

Chapter5CarbohydrateMetabolismThemajorfunctionofcarbohydrateisasafueltobeoxidizedandprovideenergyforothermetabolicprocesses.When1gramofcarbohydrateisoxidizedcompletelytoCO2andH2O,4kilocalories(66.8kJ)ofenergycanbereleased.Mostofstarchishydrolyzedtoglucoseinsmall

intestine.Glucoseisabsorbedintobloodbyintestinalepithelialcells.Duringtheabsorptiveperiodbloodsugarmayrise.Theliverisresponsiblefordecreasingtheraisedbloodsugar,andconvertingglucoseintoglycogenorfattyacids.Bloodsugarthenismaintainedatthenormallevel.Modelofamammalianglucosetransporter.Thehydrophobicityprofileoftheproteinindicates12transmembrane

helices.FamilyofglucosetransportersNameTissuelocationKmCommentsGLUT1Allmammaliantissues1mMBasalglucoseuptakeGLUT2Liverandpancreatic15~20mMInthepancreas,playsarole

cellsinregulationofinsulinIntheliver,removesexcessglucosefromthebloodGLUT3Allmammaliantissues1mMBasalglucoseuptakeGLUT4Muscleandfatcells5mMAmountinmuscleplasmamembraneincreaseswithendurancetrainingGLUT5smallintestine－PrimarilyafructosetransporterSectionIIntroduction:thefateofabsorbedglucoseGlycolytic

pathwayFormationofacetylCoAOxidativephosphorylationendSectionIIGlycolysis(AnaerobicDegradation)Thispathwayisuniversalpathway,anancientpathway,mayoccurinallhumancells.“Glycolysis”isderivedfromGreekwordsglycos(sugar,sweet)andlysis(dissolution)1-1Thedegradationofglucosetopyruvate1-2Conversionofpyruvatetolactate1.BasicprocessofglycolysiHexokinase(HK)glucokinase(GK)ATPATPend1.Glucoseastheformofglucose6-phosphateiscapturedwithincells,thephosphateestercannotpenetratethemembrane.2.TheinvestorofthisreactionisATP,whichasaphosphatedonorprovidesenergytothereaction.Energy-consumingreactionandirreversiblereaction.3.HKisakeyenzyme,canbeinhibitedbyitsproductG-6-P,andhasahighaffinity(Km=0.1mmol/L)foritssubstrate.4.Glucokinase(GK)istheisoenzymeIV,presentinliver.ThisenzymehasahigherKm(10mmol/L)foritssubstrate.4pointsforthisreaction:Km=0.1mmol/L00.12345Concentrationofbloodsugarfluctuates39mmol/Lwhichdoesnotaffectthevelocityoftheenzymaticreaction.Hexokinase

Km=about10mmol/L024681012141618GlucokinaseConcentrationofbloodsugarfluctuates39mmol/Lwhichactuallyaffectsthevelocityoftheenzymaticreaction.TurnbackVmVmBloodsugarBloodsugarAsummaryLocation:cytosolOriginalmaterial:glucoseEndproduct:lactateKeyenzymes:Hexokinase

PhosphofructokinaseI

Pyruvate

kinaseTwiceenergyredistributionswithinmolecule.Twicesubstratelevelphosphorylations,netamountsofATPproducedare2.Oncedehydrogenation:oxidationOncehydrogenation:reduction2.TheregulationofglycolysisGlucagonATPcAMPATPADPF-6-PF-2,6-BPPPPFK-2activeFBP-2inactiveFBP-2activeinactivePFK-2PiPKAATPADPPiPhosphoprotein

PhosphataseF-1,6-BPGlucoseATPADPPFK-1AMPCitrateAMPCitrate－－－HormoneregulationCovalentregulationAllostericregulationLactateAdenylate

cyclaseNextThedomainstructureofthebifunctionalenzymephosphofructokinase2.Thekinasedomain(purple)isfusedtothephosphatasedomain(red).TheknasedomainisaP-loopNTPhydrolasedomain,asindicatedbythepurpleshading.Thebarrepresentstheaminoacidsequenceoftheenzyme.PFK-23.Thesignificanceofglycolysis

Glycolysisistheemergencyenergy-yieldingpathway,suchasrun100-metersdash,climbamountain,standinghighjump..GlycolysisisthemainwaytoproduceATPinsometissues,eventhoughtheoxygensupplyissufficient,suchasredbloodcells,retina,testis,skin,medullaofkidney.Inclinicalpractice,suchasheartfailure,circulationfailure,respirationfailure,excessivelossofblood.SectionIIIAerobicoxidationofglucoseTheprocessofoxidationcompletelyfromglucosetoCO2andH2Oisnamedaerobicoxidation.Thisprocessisthemajorprocesstoprovideenergyformosttissues.Glucoseoxidationcanbedividedinto3phases:OxidationfromglucosetopyruvateincytosolOxidationfrompyruvatetoacetylCoAinmitochondriaTricarboxylicacidcycleandoxidativephosphorylation1.ThebasicprocessofaerobicoxidationofglucoseO2O2O2GlucoseG-6-PPyruvatePyruvateAcetylCoATricarboxylicacidcycleH++eCO2H2Ocytosolmitochondria1-2PyruvateoxidativecarboxylationPyruvate

dehydrogenasecomplexincluding

pyruvate

dehydrogenase(12subunits)

dihydrolipoamide

transacetylase(60subunits)

dihydrolipoamide

dehydrogenase(6subunits)TPP,NAD+,FAD,CoA,Lipoicacid,1-1TheoxidationofglucosetopyruvateMg2+(a)Electronmicrographofthepyruvate

dehydrogenasecomplexisolatedfromE.coli,showingitssubunitstructure.(b)Interpretivemodeloftheorganizationofthemam-malian

pyruvate

dehydrogenasecomplex.The24E2subunitsaredepictedashavinganinnercatalyticdomain(green)withanattachedflexiblelipoyllysyldomain(red)andanE1/E3bindingdomain(blue)joinedbylinkersegments(gray).Thecomplexalsocontains24dimericE1components(orange)and6dimericE3components(yellow).NotethatthemammaliancomplexislargerandhasmoresubunitsthantheE.colicomplex.Pyruvate+NAD++HSCoAAcetylCoA+NADH+H++CO2Pyruvate

dehydrogenasecomplexend1-3TricarboxylicacidcycleThefirstreactioninTCACisthecondensationofacetyl-CoAandoxaloacetatetoformcitrate.TheTCACisalsonamedcitratecycle.-ketoglutarateend

TricarboxylicacidcycleisalsonamedKrebscycleforthememoryofthediscoverHansKrebs.HansKrebswasoneofthegreatpioneersofmodernbiochemistry.HewasborninGermanyandreceivedhismedicaleducationthere.In1932,whenhewasanassistantinmedicine,heworkedouttheureacyclewithamedicalstudent.In1937,hediscovered"tricarboxylicacidcycle"inEngland.From1954onhewastheheadoftheDepartmentofBiochemistryatOxford.Hewasretiredfromthatpositionin1967.Hewasstillworkingactivelyuntilhisdeathin1981.The"tricarboxylicacidcycle"hasbeenregardedasthemostimportantsinglediscoveryinthehistoryofmetabolicbiochemistry.

TableIII-1generationofATPinaerobicoxidationofglucoseTotalpermoleofglucoseunderaerobicconditions:38ATP

pathwayReactionsCatalyzedbyMethodsofATPproductionMolesofATPformedpermolofglucoseGlyceraldehyde3-phosphate

dehydrogenaseGlycolyticpathwayRespiratorychainOxidationof2NADH6Phosphoglycerate

kinasePhosphorylationatsubstratelevel2Pyruvate

kinasePhosphorylationatsubstratelevel2AllowforconsumptionofATPbyreactionscatalyzedbyhexokinaseandphosphofructokinase-2ProductionofacetylCoAPyruvate

dehydrogenasecomplexRespiratorychainOxidationof2NADH6TricarboxylicacidcycleIsocitrate

dehydrogenaseAlpha-ketoglutarateDehydrogenasecomplexSuccinyl

CoA

synthetaseSuccinate

dehydrogenaseMalate

dehydrogenaseRespiratorychainOxidationof2NADHRespiratorychainOxidationof2NADHPhosphorylationatsubstratelevelRespiratorychainOxidationof2FADH2RespiratorychainOxidationof2NADH66462TheregulationofaerobicoxidationInhibitorsEnzymesActivatorsCytosol

HexokinaseGlucose6-phosphateATP,citrate6-phosphofructokinase-1(Covalentmodification)AMP,ADP,fructose1,6-biphosphateFructose2,6-biphosphateATP,alanine

pyruvate

kinase(Covalentmodification)fructose1,6-biphosphateMitochondriaAcetylCoA/CoA,NADH/NADATP/ADP,NADH/NADATP/ADP,NADH/NADpyruvate

dehydrogenase(covalentmodification)isocitrate

dehydriogenase-ketoglutarate

dehydrogenaseAMP,CaADP,Ca+Ca+SectionIVThePentosePhosphatePathway(PPP)Location:cytosolOriginalmaterial:glucose6-phosphateEndproduct:theintermediateproductsofglycolysisThecoenzymeofdehydrogenation:NADP+

1.Thebasicprocess:Oxidativephase(formationofpentosephosphate)Non-oxidativephase(grouptransferring)endC5+C5C3+C7transketolaseC3+C7C4+C6transaldolaseC4+C5C3+C6transketolaseC5+C5+C5C3+C6+C63CO26NADP+3G6-PC5+C5+C5C3+C6+C66NADPH+H+2.ThesignificanceofPPP2-1Ribose5-phosphate2-2NADPH

1)Reducingpowerforbiosynthesisoffattyacids,cholesterol,andsoon.2)Coenzymeofglutathionereductasetokeepthenormallevelofreducedglutathione.

3)NADPHservesasthecoenzymeofmixedfunctionoxidases(mono-

oxygenases).Biotransformation.DeficienciesofcertainenzymesofthePPParemajorcausesofhemolysisofredbloodcells,resultinginonetypeofhemolyticanemia.Thereare100millionpeopleintheworldhavethedeficiencyofglucose6-phosphatedehydrogenase.Whenthesusceptiblepeopletakesomemedicinesuchasantimalarial

primaquine,aspirin,orsulfonamide,oreatbroadbean(favabean),hemolysiscanbemanifested.PeoplemaysufferfromjaundiceendSectionVglycogenFormationandDegradationGlycogengranulesHighsolubilityandmorereactivepointsforsynthesisanddegradationglycogenprimer1.GLYCOGENESIS2.GLYCOGENOLYSISendGlycogenesisendGlycogenolysis14glucose1-phosphate12glucose1-phosphate1glucosephosphorylaseaphosphorylaseaglucan

transferaseglucosidasephosphorylaseaend

3.RegulationofGlycogenesisandGlycogenolysisend4.Thesignificanceof

glycogenesisandglycogenolysisLiverglycogen(asmuchas10%ofliverwetweight)functionsasaglucosereserveformaintainingbloodglucoseconcentration.Muscleglycogen(total400gram)servesasafuelreserveforsynthesisofATPwithinthattissue.SectionVIGluconeogenesis

Theprocessoftransformationofnon-carbohydratestoglucoseorglycogenistermedasgluconeogenesis.1.Thebasicprocessofgluconeogenesisessentiallyareversalofglycolysiswiththreebarrierscircumventedbyfouradditionalenzymes:

1)frompyruvatetophosphoenolpyruvate:

pyruvate

carboxylase

phosphoenol

pyruvate

carboxykinase2)fromfructose1,6-phosphatetofructose6-phosphate

fructose1,6-bisphosphatase3)fromglucose6-phosphatetoglucose

glucose6-phosphataseGlcG-6-PF-6-PF-1,6BPGAP1,3-BPG3-PG2PGPEPLactatePyruvateDHAPOxaloacetate1-1Theconversionofpyruvatetophosphoenol

pyruvate

1-2Theconversionoffructose1,6-bisphosphatetofructose6-phosphate1-3Theconversionofglucose6-phosphatetoglucoseSubstratecycleorfutilecycle:nothingisaccomplishedbutthewasteofthedifferencebetweentheATPformationinonedirectionandthatrequiredintheoppositedirection.

Bumblebeemustmaintainathoracictemperatureofabout30°Ctofly.Abumblebeeisabletomaintainthishighthoracictemperatureandforageforfoodevenwhentheambienttemperatureisonly10°Cbecausephosphofructokinaseandfructose1,6-bisphosphataseinitsflightmusclearesimultaneouslyhighlyactive;thecontinuoushydrolysisofATPgeneratesheat.Incontrast,thehoneybeehasalmostnofructose1,6-bisphosphataseinitsflightmuscleandconsequently