《医学分子生物学》讲义 铁的代谢平衡与调节.pptVIP

******************Transferrinreceptor(TfR,运铁蛋白受体)homodimerictransmembraneprotein.Foundinmostcells.Mostdenseonerythroidprecursors,hepatocytes,placentalcellsTfRFerroportin(FPN/膜铁转运蛋白)IronexporterDivalentmetaltransporterprotein1(DMT1,二价金属离子转运蛋白）*ThetransferrincycleDmt1*ErythropoiesisisirondependentEachhemoglobinmolecule=4ironatoms5litersblood=2.4litersRBC=2.4giron120dRBClifespan=need2400mg/120d

=20mg/dayironforbaselineerythropoiesis*MacrophageironrecyclingFerroportinCerulo-plasminFe2+Fe3+TfFeFerritinFeHeme*ironstorageFerritincomplex24subunitsEachferritincomplexcanstoreabout4000iron(Fe3+)ionsControlironadministrationhemosiderin*体内铁指标检测间接指标：ferritin,transferrinsaturation直接检测：a.比色法/组织干重(ie,liverironcontent)b.染色法(thePrussianbluereaction)c.活体显微成像法(FerriScan)IronPrussianbluestaining*FerriScanPERSISTENTSERUMFERRITINLEVEL1000ng/mlorworst2500ng/mlwithoutanyothersignsofinflammation.THESESTATEMENTSAREBASEDONRETROSPECTIVEANDPROSPECTIVESURVIVALSTUDIES(BorgnaPignattietal.Haematologica2004;OlivieriNFetal.NEJM1994;Maggioetal.BloodCellsMolDis2009)LIVERIRONCONCENTRATION3.2mg/gr/driedweightor57,14microM/g/driedweight.THISSTATEMENTISBASEDONHEREDITARYHEMOCHROMATOSISCLINICALSTUDIES(OlivieriNFandBritthenamGM,Blood1997)CommonDefinitionofIronOverload*二、铁平衡调节MechanismsofIronHomeostasisIntracellularDominatedbytheIRE-IRPmechanismExtracellularDominatedbyhepcidin/ferroportininteractionsIntracellularandextracellularmechanismsmayinteract*IntracellularregulationofIronHomeostasisDominatedbytheIRE-IRPmechanismiron-responsiveelements(IRE)iron-responsiveproteins(IRP)IRP1andIRP2–cytosolicRNAbindingproteins.Bindtoiron-responsiveelementslocatedin5’or3’untr