binding of oxygen to hemoglobin与氧结合的血红蛋白

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1、Lecture11:09-15-06Bindingofoxygentohemoglobin,sicklecellanemia,andbeta-thalassemia.Thereactionofoxygenbindingtohemoglobininacooperativemannerisgivenbythefollowingequation:1.Cooperativebindingofoxygenbyhemoglobinrequiresthatthebindingofoxygenatonesiteinthehemoglobintetramerinfluencetheox

2、ygenbindingpropertiesattheothersites.2.Variousmodelsexplainthecooperativebindingofoxygentohemoglobin.3.Thecooperativebindingofoxygenhelpsdeliveroxygentotissueswhereitismostneeded.4.TheoxygenbindingtohemoglobinistightlyregulatedbypHandCO2concentrationinblood.5.ThiseffectiscalledasBohr’se

3、ffectnamedafterthescientistChristianBohr.6.TheoxygenaffinityofhemoglobingoesdownasthepHdecreasesfrom7.47.Consequently,thetendencytoreleaseoxygenincreaseswithadecreaseinpHbelow7.4.TheabovefigureillustratestheeffectofpHonoxygenbindingtohemoglobin.WhatisthechemicalbasisfortheeffectofpH?1.V

4、al-His-Leu-Thr-Pro-Glu-Glu-LysThisistheaminoacidsequenceofthefirst8aminoacidsintheN-terminusofhemoglobin2.TheinteractionofthesidechainofhistidinewithanegativelychargedglutamateinthesamechainformsasaltbridgeatacidicpHwheretheimidazolegroupofhistidineisprotonated.3.Athigh(alkaline)pHthesi

5、dechainofhistidineisnotprotonatedandthuscannotformsaltbridge.4.Anymutationsingenesencodinghemoglobinsubunitscanresultindisease.eg:sicklecellanemia,beta-thalassemiaetc.5.Sicklecellanemiaresultsfromabnormalsickleshapeofredbloodcells.6.Itiscausedduetothevariationintheaminoacidsequenceofone

6、hemoglobinchain.7.Asingleaminoacidsubstitutuioninbetachainofhemoglobini.eavalineresidueissubstitutedinsteadofglutamateresidueinposition6andhencethereisnosaltbridgeformed.1.Themutatedformisreferredtoashemoglobin–S.2.Thesubstitutedhydrophobicvalineresidueinteractswithotherhydrophobicresid

7、uesphenylalanineandvalineoftheneighboringbetachaintoinitiateaggregationofhemoglobin.3.Inthalassemiathereisasubstantialreductionofasinglehemoglobinchain.Basedonthereductionofaparticularchainitiscalledaseitheralphaorbetathalassemia.4.Asaresultofinsufficientquantityofoneofthechain