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Arsenicpoisoningmechanismandtargets
(LastUpdatedOn:April4,2020)
Ashortintroduction
ArsenicpoisoningisatypeoffoodpoisoningthatoccursduetotheingestionoffoodscontaminatedwithArsenicionsandcompoundscontainingArsenic.Arsenicpoisoningorarsenicosisisknownsinceancienttimesthoughitsmechanismwasunknownuntiltheeraofmedicaladvancements.ArsenicisanelementthatbelongstotheNitrogenfamily.Itshowstwovalencieswhileformingacompound;trivalentaswellaspentavalentcompounds.As(III)compoundssuchasarsenite(AsO33-),organicarsenicalsandAs(IV)compoundssuchasArsenate(AsO43-)aretoxic.That’sbecausetheybindtodifferentmetabolicintermediates.Uponbinding,thesecompoundsuncoupleorhaltingthekeyreactions.TheultimateresultoftheArsenicpoisoningisthestoppageofrespirationandfinally,ATPproductionisalsostopped.
Differentarseniccompounds
Differenttargetsofanarsenicpoisoning
Glycolyticpathway.
Pyruvatedehydrogenasecomplex.
α-ketoglutaratedehydrogenasecomplexofTCAcycle
Arsenicpoisoninginglycolysis
Arsenate(AsO43-)isananalogofinorganicphosphate.DuringanArsenicpoisoning,?glycolysis?continuestoproducepyruvate;however,thereisnonetproductionofATP.ThatisbecauseArsenatereactswiththeglyceraldehyde-3-phosphatetoform1-arseno,3-phosphoglycerate.
Glyceraldehydephosphatedehydrogenase(GAPDH)isanenzymethatconvertsglyceraldehyde-3-phosphateto1,3-bisphosphoglycerate.However,itcanalsocatalyzethereactionbetweenArsenateandglyceraldehyde-3-phosphate.ArsenateactuallycompeteswiththeinorganicphosphatefortheGAPDH.
Innormalconditions,GAPDHconvertsglyceraldehydes-3-phosphateto1,3-biosphosphoglycerate.Afterthat,Phosphoglyceratekinaseconverts1,3-bispohsophglycerateto3-phosphoglycerate,releasingonemoleculeofATP.However,whenthereisanarsenate,GAPDHconvertsglyceraldehyde-3-phosphateto1-arseno,3-phospho
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