生物化學(xué) 第十講 Biomembrane Transport-2

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

ActivetransportBasic

conceptsPassivetransportersChannelsExamplesofionchannelfunctions11.Basicconceptstransporttypes2Energychangesaccompanyingpassageofahydrophilicsolutethroughthelipidbilayerofabiomembrane1.Basicconcepts(ctnd)3一個(gè)環(huán)形肽纈氨霉素(valinomycin)的抗菌機(jī)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大學(xué)的PeterAgre研究小組設(shè)法從血細(xì)胞膜上提純Rh抗原的32kDa單元時(shí)發(fā)現(xiàn)了一種分子量為28kDa的物質(zhì)總是會(huì)被一同提純出來。他們起初以為這是Rh蛋白的降解產(chǎn)物。后來意識(shí)到這是一種以前沒有被發(fā)現(xiàn)的蛋白。PeterAgre研究小組設(shè)計(jì)了一個(gè)非常巧妙的實(shí)驗(yàn)，他們用微管注入的方法將CHIP28的mRNA注入到蛙卵細(xì)胞內(nèi),從而將該蛋白表達(dá)到了蛙卵細(xì)胞膜上。在溶液中加入高滲透壓介質(zhì)后,表達(dá)了CHIP28的蛙卵細(xì)胞迅速膨脹直至破裂,而沒有表達(dá)CHIP28的細(xì)胞則幾乎沒有變化。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認(rèn)識(shí)有限，目前了解較多的是一種細(xì)菌中的鉀離子通道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(腰鞭毛蟲)

Voltage-gatedK+channelsDendrotoxin(樹木毒素)producedbyblackmambasnake(樹眼睛蛇)Ach-gatedionchannelsTubocurarine(筒箭毒堿)istheactivecomponentofcurare([植]箭毒馬鞍子)Cobrotoxin(眼鏡蛇毒素),andbungarotoxin