生物化学 第十讲 Biomembrane Transport-2

§10Biomembrane&Transport§10.1Introduction§10.2Passivetransport§10.3

ActivetransportBasic

conceptsPassivetransportersChannelsExamplesofionchannelfunctions11.Basicconceptstransporttypes2Energychangesaccompanyingpassageofahydrophilicsolutethroughthelipidbilayerofabiomembrane1.Basicconcepts(ctnd)3一个环形肽缬氨霉素(valinomycin)的抗菌机理45Classesoftransporters(permeases)Channels(gate-like)Carriers(enzyme-like)PassivetransportersActivetransportersPrimaryactivetransporters(needATPorlight)Secondaractivetransporters(needelectrochemicalgradientdirectly,ATPindirectly)1.Basicconcepts(ctnd)6§10Biomembrane&Transport§10.1Introduction§10.2Passivetransport§10.3

ActivetransportBasicconceptsPassivetransportersChannelsExamplesofionchannelfunctions72.Passivetransporters(2)

Cl--HCO3-exchanger(1)

GlucosetransportersGLUTKtTissueRoleGLUT11.5mMUbiquitousBasalglucoseuptakeGLUT266mMLiver,pancreaticisiets,intestineInliver,removalofexcessglucosefromblood;inpancreas,regulationofinsulinreleaseGLUT3-Brain(neuronal)BasalglucoseuptakeGLUT45mMMuscle,fat,heartActivityincreasedbyinsulinGLUT5-Intestine,testis,kidney,spermPrimarilyfructosetransportGLUT6，GLUT7，GLUT9，GLUT10，GLUT11，GLUT12Theconcentrationofglucoseinbloodis4.5to5mM108TopologyofGLUTs9StructureofthetransmembranehelexofGLUTsFourTMhelexesinthecenterofGLUTs10TransportModelofGLUTs11KineticsofGLUTs12Insulinregulatestheglucoselevelinblood513IncreasesthepermeabilityoftheerythrocytemembranetoHCO3-

byafactorofmorethanamillion;AllowstheentryandexitofHCO3-withoutchangesinthetransmembraneelectricalpotential.Chloride-bicarbonateexchanger14§10Biomembrane&Transport§10.1Introduction§10.2Passivetransport§10.3

ActivetransportBasicconceptsPassivetransportersChannelsExamplesofionchannelfunctions153.Channels(1)H2Ochannels(2)IonchannelsLigand-gatedionchannels:2,3,4Voltage-gatedionchannels:1(3)Ionselectivity

inchannels16ligand-gatedionchannelsPlaceLigandsChannelforextracellularAcetylcholineNa+，K+，Ca2+Serotonin血清素(5-hydroxytryptamine)Na+，K+，Ca2+glutamateNa+，K+，Ca2+glycineCl－g-aminobutyricacid(GABA)Cl－，K+Intracellular（secondmessengers）cAMPK+，Ca2+cGMPNa+，Ca2+IP3Ca2+Ca2+Cl－1780年代中期,JohnHopkins大学的PeterAgre研究小组设法从血细胞膜上提纯Rh抗原的32kDa单元时发现了一种分子量为28kDa的物质总是会被一同提纯出来。他们起初以为这是Rh蛋白的降解产物。后来意识到这是一种以前没有被发现的蛋白。PeterAgre研究小组设计了一个非常巧妙的实验，他们用微管注入的方法将CHIP28的mRNA注入到蛙卵细胞内,从而将该蛋白表达到了蛙卵细胞膜上。在溶液中加入高渗透压介质后,表达了CHIP28的蛙卵细胞迅速膨胀直至破裂,而没有表达CHIP28的细胞则几乎没有变化。Waterchannels18CHIP28renamedasaquaporin1(AQP1)1920AQPsalwaysformtetramersinthecellmembrane,andeachsubunitscanfacilitatethetransportofwaterand,insomecases,othersmallsolutesacrossthemembrane21Topologyofasubunit22tetramersWaterchannelformedbyasubunit23H2OselectivityofAQP24

Acetylcholine-gatedionchannelsThischannelallowsreadypassagetoNa+,Ca2+andK+,butothercationsandallanionsareunabletopass25StructureofAch-gatedChannela,b,g,dsubunitsarehomologous26CationselectivityofAch-gatedchannel27Open-closemechanismofAch-gatedchannel28Na+channelismadeupofanaandabsubunitIIIIIIIVVoltage-gatedNa+ionchannels29Allvoltage-gatedionchannelshaveasimilaraarchitecture

S4–relatedtovoltagesensing,

isfoundinallvoltagegatedionchannelsandisabsentinligandgatedchannels

aSubunitofNa+channel30Architectureofa

subunitinmembrane31FunctionsofS4andS632443334FourasubunitscomplexoftheK+channelinratbraincells(fourbsubunitsnotshow)35S4(theArg-containinghelix)maketheK+channelvoltage-sensitive(fourbsubunitsnotshow)outsideinside36OpenorclosedstateoftheK+channelinratbraincells(fourbsubunitsnotshow)37FouridenticalsubunitsIonselectivityinchannels认识有限，目前了解较多的是一种细菌中的钾离子通道38ModeloftheK+channelofbacteria39SelectivityfilterofbacterialK+channel40SelectivityfilterofbacterialK+channel(ctnd)41§10Biomembrane&Transport§10.1Introduction§10.2Passivetransport§10.3

ActivetransportBasicconceptsPassivetransportersChannelsExamplesofionchannelfunctions42RestingMembranePotential434445ActionPotential462947PropagationofActionPotentialsinNerveFiber4849Synaptictransmission5051VisionBipolarcellBipolarcell52535411-cis-retinalGprotein5556Olfaction57Gustation58SomeinhibitorsofionchannelsVoltage-gatedNa+channelsTetrodotoxin(河豚毒素)producedbypufferfish(河豚)Saxitoxin(蛤蚌毒素)producedbymarinedinoflagellate(腰鞭毛虫)

Voltage-gatedK+channelsDendrotoxin(树木毒素)producedbyblackmambasnake(树眼睛蛇)Ach-gatedionchannelsTubocurarine(筒箭毒碱)istheactivecomponentofcurare([植]箭毒马鞍子)Cobrotoxin(眼镜蛇毒素),andbungarotoxin