11 membrane transport of small

1、InThisChapterPRINCIPLESOFMEMBRANETRANSPTTRANSPTERSACTIVEMEMBRANETRANSPTIONCHANNELSTHEELECTRICALPROPERTIESOFMEMBRANES11:1Becauseofitshyhobicinterithelipidbilayerofcellmembranespreventsthepassageofmostpolarmolecules.Thisba

2、rrierfunctionallowsthecelltomaintainconcentrationsofsolutesinitscytosolthatdifferfromthoseintheextracellularfluidineachoftheintracellularmembraneenclosedcompartments.Tobenefitfromthisbarrierhowevercellshavehadtoevolveway

3、softransferringspecificwatersolublemoleculesionsacrosstheirmembranesindertoingestessentialnutrientsexcretemetabolicwasteproductsregulateintracellularionconcentrations.Cellsusespecializedtransmembraneproteinstotransptinga

4、nicionssmallwatersolubleganicmoleculesacrossthelipidbilayer.Cellscanalsotransfermacromoleculesevenlargeparticlesacrosstheirmembranesbutthemechanismsinvolvedinmostofthesecasesdifferfromthoseusedftransferringsmallmolecules

5、theyarediscussedinChapters1213.Theimptanceofmembranetransptisreflectedinthelargenumberofgenesinallganismsthatcodeftransptproteinswhichmakeup15–30%ofthemembraneproteinsinallcells.Somespecializedmammaliancellsdevoteuptotwo

6、thirdsoftheirtotalmetabolicenergyconsumptiontomembranetransptprocesses.Webeginthischapterbydescribingsomegeneralprinciplesofhowsmallwatersolublemoleculestraversecellmembranes.Wethenconsiderinturnthetwomainclassesofmembra

7、neproteinsthatmediatethistrafficofmoleculesbackfthacrosslipidbilayers:transpterswhichhavemovingpartstotransptspecificmoleculesacrossmembraneschannelswhichfmanarrowhyhilicpeallowingpassivetransmembranemovementprimarilyofs

8、mallinganicions.Transpterscanbecoupledtoasourceofenergytocatalyzeactivetransptacombinationofivepassivepermeabilityactivetransptcreateslargedifferencesinthecompositionofthecytosolcomparedwiththatofeithertheextracellularfl

9、uid(Table11–1)thefluidwithinmembraneenclosedganelles.Bygeneratingionicconcentrationdifferencesacrossthelipidbilayercellmembranescanstepotentialenergyinthefmofelectrochemicalgradientswhichdrivevarioustransptprocessesconve

10、yelectricalsignalsinelectricallyexcitablecells(inmitochondriachloplastsbacteria)makemostofthecell’sATP.Wefocusourdiscussionmainlyontransptacrosstheplasmamembranebutsimilarmechanismsoperateacrosstheothermembranesoftheeuca

11、ryoticcellasdiscussedinlaterchapters.Inthelastpartofthechapterweconcentratemainlyonthefunctionsofionchannelsinneurons(nervecells).Inthesecellschannelproteinsperfmattheirhighestlevelofsophisticationenablingwksofneuronstoc

12、arryoutallthehumanbrain’sastonishingfeats.PRINCIPLESOFMEMBRANETRANSPTWebeginthissectionbydescribingthepermeabilitypropertiesofproteinfreesyntheticlipidbilayers.Wethenintroducesomeofthetermsusedtodescribethevariousfmsofme

13、mbranetransptsomestrategiesfacterizingtheproteinsprocessesinvolved.26thFebruary2007:FinalpagesChapter1111MembraneTransptofSmallMoleculestheElectricalPropertiesofMembranesAllmembranetransptproteinsthathavebeenstudiedindet

14、ailhavebeenfoundtobemultipasstransmembraneproteins—thatistheirpolypeptidechainstraversethelipidbilayermultipletimes.Byfmingacontinuousproteinpathwayacrossthemembranetheseproteinsenablespecifichyhilicsolutestocrossthememb

15、ranewithoutcomingintodirectcontactwiththehyhobicinteriofthelipidbilayer.Transpterschannelsarethetwomajclassesofmembranetransptproteins(Figure11–3).Transpters(alsocalledcarrierspermeases)bindthespecificsolutetobetranspted

16、undergoaseriesofconfmationalchangestotransfertheboundsoluteacrossthemembrane.Channelsincontrastinteractwiththesolutetobetransptedmuchmeweakly.Theyfmaqueouspesthatextendacrossthelipidbilayerwhenopenthesepesallowspecificso

17、lutes(usuallyinganicionsofappropriatesizege)topassthroughthemtherebycrossthemembrane.Notsurprisinglytransptthroughchannelsoccursatamuchfasterratethantransptmediatedbytranspters.Althoughwatercandiffuseacrosssyntheticlipid

18、bilayersallcellscontainspecificchannelproteins(calledwaterchannelsaquapins)thatgreatlyincreasethepermeabilityofthesemembranestowateraswediscusslater.ActiveTransptIsMediatedbyTransptersCoupledtoanEnergySourceAllchannelsma

19、nytransptersallowsolutestocrossthemembraneonlypassively(“downhill”)aprocesscalledpassivetransptfacilitateddiffusion.Inthecaseoftransptofasingleungedmoleculethedifferenceintheconcentrationonthetwosidesofthemembrane—itscon

20、centrationgradient—drivespassivetransptdeterminesitsdirection(Figure11–4A).Ifthesolutecarriesagehoweverbothitsconcentrationgradienttheelectricalpotentialdifferenceacrossthemembranethemembranepotentialinfluenceitstranspt.

21、Theconcentrationgradienttheelectricalgradientcombinetofmadrivingfcetheelectrochemicalgradientfeachgedsolute(Figure11–4B).WediscusselectrochemicalgradientsinmedetailinChapter14.Infactalmostallplasmamembraneshaveanelectric

22、alpotentialdifference(voltagegradient)acrossthemwiththeinsideusuallynegativewithrespecttotheoutside.Thispotentialdifferencefavstheentryofpositivelygedionsintothecellbutopposestheentryofnegativelygedions.PRINCIPLESOFMEMBR

23、ANETRANSPT11:3Figure11–2Permeabilitycoefficientsfthepassageofvariousmoleculesthroughsyntheticlipidbilayers.Therateofflowofasoluteacrossthebilayerisdirectlyproptionaltothedifferenceinitsconcentrationonthetwosidesofthememb

24、rane.Multiplyingthisconcentrationdifference(inmolcm3)bythepermeabilitycoefficient(incmsec)givestheflowofsoluteinmolespersecondpersquarecentimeterofbilayer.Aconcentrationdifferenceoftryptophanof10–4molcm3(10–410–3L=0.1M)f

25、examplewouldcauseaflowof10–4molcm310–7cmsec=10–11molsecthrough1cm2ofbilayer6104moleculessecthrough1mm2ofbilayer.10_1410_1210_1010_810_610_410_2H2OureaglyceroltryptophanglucoseCI_KNalowpermeabilityhighpermeabilityFigure11

26、–3Transpterschannelproteins.(A)Atranspteralternatesbetweentwoconfmationssothatthesolutebindingsiteissequentiallyaccessibleononesideofthebilayerthenontheother.(B)Incontrastachannelproteinfmsawaterfilledpeacrossthebilayert