MembraneTransport膜轉運XiaQiang（夏強）,PhDDepartmentofPhysiologyRoomC518,BlockC,ResearchBuilding,SchoolofMedicineTel:88208252Email:xiaqiang@ObjectiveHowmoleculesandionsgetandoutofcells?OrganelleshavetheirownmembranesCellMembrane(plasmamembrane)PhospholipidbilayerLipidsProteinsCarbohydratesMembraneproteinsIntegral(intrinsic)proteins Peripheral(extrinsic)proteinsIntegralproteinPeripheralproteinFunctionsofmembraneproteinsAdhesionSomeglycoproteinsattachtothecytoskeletonandextracellularmatrix.CarbohydratesGlycoprotein GlycolipidProteinssynthesizedonendoplasmicreticulummembrane-boundribosomeswouldbeexpectedtoendupinAThecytosolBPeroxisomesCThenucleusDSecretoryvesiclesEThemitochondriaProteinssynthesizedonendoplasmicreticulummembrane-boundribosomeswouldbeexpectedtoendupinAThecytosolBPeroxisomesCThenucleusDSecretoryvesiclesEThemitochondriaWhichofthefollowingorganellesisthemajorsiteforanaerobicmetabolism?AMitochondriaBCytoplasmCGolgiapparatusDNucleolusECentriolesWhichofthefollowingorganellesisthemajorsiteforanaerobicmetabolism?AMitochondriaBCytoplasmCGolgiapparatusDNucleolusECentriolesWhichofthefollowingcellstructuresisresponsibleforthesynthesisofmultiplesubstancesandstructures?ANucleusBRibosomeCEndoplasmicreticulumDMitochondriaELysosomeWhichofthefollowingcellstructuresisresponsibleforthesynthesisofmultiplesubstancesandstructures?ANucleusBRibosomeCEndoplasmicreticulumDMitochondriaELysosomeMembraneTransportLipidBilayer--primarybarrier,selectivelypermeableMembraneTransportSimpleDiffusion（單純擴散）FacilitatedDiffusion（易化擴散）ActiveTransport（主動轉運）EndocytosisandExocytosis（出胞與入胞）Overtime,solutemoleculesplacedinasolventwillevenlydistribute

themselves.START:Initiallyhigherconcentrationofmoleculesrandomlymovetowardlowerconcentration.Diffusional

equilibriumistheresult

(Partb).AttimeB,someglucosehascrossedintoside2assomecrossintoside1.Note:thepartitionbetweenthetwocompartmentsisamembranethatallowsthissolutetomovethroughit.Netfluxaccountsforsolutemovementsinbothdirections.SimpleDiffusionRelativetotheconcentrationgradient movementisDOWNtheconcentrationgradientONLY(higherconcentrationtolowerconcentration)RateofdiffusiondependsonTheconcentrationgradientChargeonthemoleculeSizeLipidsolubilityFacilitatedDiffusionCarrier-mediatedInsimplediffusion,fluxrateislimitedonlybytheconcentrationgradient.Incarrier-mediatedtransport,thenumberofavailablecarriersplacesanupperlimitonthefluxrate.Characteristicsofcarrier-mediateddiffusionnetmovementalwaysdependsontheconcentrationgradient

SpecificitySaturationCompetitionChannel-mediated3cartoonmodelsofintegralmembraneproteinsthatfunctionasionchannels;theregulatedopeningandclosingofthesechannelsisthebasisofhowneuronsfunction.Theopeningandclosingofionchannelsresultsfromconformationalchangesinintegralproteins.Discoveringthefactorsthatcausethesechangesiskeytounderstandingexcitablecells.CharacteristicsofionchannelsSpecificityGating（門控）Threetypesofpassive,non-coupledtransportthroughintegralmembraneproteinsOutsideInsideNH2CO2HIIIIIIIV++++++++++++Voltage-gatedChannele.g.Voltage-dependentNa+channelNa+channelNa+channelBalloonfishorfuguClosed Activated InactivatedNa+channelconformationOpen-stateClosed-stateLigand-gatedChannele.g.N2-AChreceptorchannelAquaporinAquaporinsarewaterchannelsthatexcludeionsAquaporinsarefoundinessentiallyallorganisms,andhavemajorbiologicalandmedicalimportance

TheNobelPrizeinChemistry2003"fordiscoveriesconcerningchannelsincellmembranes"PeterAgre

RoderickMacKinnon

"forthediscoveryofwaterchannels""forstructuralandmechanisticstudiesofionchannels"Thedividingwallbetweenthecellandtheoutsideworld–includingothercells–isfarfrombeinganimperviousshell.Onthecontrary,itisperforatedbyvariouschannels.Manyofthesearespeciallyadaptedtoonespecificionormoleculeanddonotpermitanyothertypetopass.Heretotheleftweseeawaterchannelandtotherightanionchannel.PeterAgre’sexperimentwithcellscontainingorlackingaquaporin.TheaquaporinisnecessaryformakingthecellabsorbwaterandswellPassageofwatermoleculesthroughtheaquaporinAQP1.Becauseofthepositivechargeatthecenterofthechannel,positivelychargedionssuchasH3O+,aredeflected.Thispreventsprotonleakagethroughthechannel.ModelforwaterpermeationthroughaquaporinInbothsimpleandfacilitateddiffusion,solutesmoveinthedirectionpredictedbytheconcentrationgradient.Inactivetransport,solutesmoveoppositetothedirectionpredictedbytheconcentrationgradient.membraneActivetransportPrimaryactivetransport（原發性主動轉運）Secondaryactivetransport（繼發性主動轉運）PrimaryActiveTransportmakingdirectuseofenergyderivedfromATPtotransporttheionsacrossthecellmembraneHere,intheoperationoftheNa+-K+-ATPase,alsoknownasthe“sodiumpump,”eachATPhydrolysismovesthreesodiumionsoutof,andtwopotassiumionsinto,thecell.

Na-KPumpelectrogenicpump（生電性泵）PhysiologicalroleofNa+-K+pumpMaintainingtheNa+andK+gradientsacrossthecellmembranePartlyresponsibleforestablishinganegativeelectricalpotentialinsidethecellControllingcellvolumeProvidingenergyforsecondaryactivetransportOtherprimaryactivetransportPrimaryactivetransportofcalciumPrimaryactivetransportofhydrogenionsSecondaryActiveTransportTheiongradientsestablishedbyprimaryactivetransportpermitsthetransportofothersubstancesagainsttheirconcentrationgradientsCotransport（同向轉運）theionandthesecondsolutecrossthemembraneinthesamedirection(e.g.Na+-glucose,Na+-aminoacidcotransport)Countertransport（逆向轉運）theionandthesecondsolutemoveinoppositedirections(e.g.Na+-Ca2+,Na+-H+exchange)CotransportersExchangersIongradients,channels,andtransportersinatypicalcellHere,wateristhesolvent.Theadditionofsolutelowersthewaterconcentration.Additionofmoresolutewouldincreasethesoluteconcentrationandfurtherreducethewaterconcentration.Solvent+Solute=SolutionOsmosis（滲透）Begin:Thepartitionbetweenthecompartmentsispermeabletowaterandtothesolute.Afterdiffusionalequilibriumhasoccurred:Movementofwaterandsoluteshasequalizedsoluteandwaterconcentrationsonbothsidesofthepartition.Begin:Thepartitionbetweenthecompartmentsispermeabletowateronly.Afterdiffusionalequilibriumhasoccurred:Movementofwateronlyhasequalizedsoluteconcentration.RoleofNa-KpumpinmaintainingcellvolumeResponsetocellshrinkingResponsetocellswellingEndocytosisandExocytosisAlternativefunctionsofendocytosis:Transcellulartransport2. Endosomalprocessing3. Recyclingthemembrane4. DestroyingengulfedmaterialsEndocytosisExocytosisTwopathwaysofexocytosisConstitutiveexocytosispathway--ManysolubleproteinsarecontinuallysecretedfromthecellbytheconstitutivesecretorypathwayRegulatedexocytosispathway--SelectedproteinsinthetransGolginetworkaredivertedintosecretoryvesicles,wheretheproteinsareconcentratedandstoreduntilanextracellularsignalstimulatestheirsecretionStepstoexocytosisVesicletrafficking:Inthisfirststep,thevesiclecontainingthewasteproductorchemicaltransmitteristransportedthroughthecytoplasmtowardsthepartofthecellfromwhichitwillbeeliminatedVesicletethering:Asthevesicleapproachesthecellmembrane,itissecuredandpulledtowardsthepartofthecellfromwhichitwillbeeliminatedVesicledocking:Inthisstep,thevesiclecomes