title: Enzymatic reduction of arsenic compounds in mammalian systems: reduction of arsenate to arsenite by human liver arsenate reductase.
abstract: An arsenate (As(V)) reductase has been partially purified from human liver. Its apparent molecular mass is approximately 72 kDa. The enzyme required a thiol and a heat stable cofactor for activity. The cofactor is less than 3 kDa in size. The thiol requirement can be satisfied by dithiothreitol (DTT). However, the extent of stimulation of reductase activity by glutathione, thioredoxin, or reduced lipoic acid was negligible compared to that of DTT. The heat stable cofactor does not appear to be Cu(2+), Mn(2+), Zn(2+), Mg(2+), or Ca(2+). The enzyme does not reduce monomethylarsonic acid (MMA(V)). The isolation and characterization of this enzyme demonstrates that in humans, the reduction of arsenate to arsenite is enzymatically catalyzed and is not solely the result of chemical reduction by glutathione as has been proposed in the past.
authors.affiliation: Graduate Interdisciplinary Program in Genetics and Department of Molecular and Cellular Biology, The University of Arizona, Tucson, Arizona 85721, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Radabaugh
authors.forename: H V
authors.initials: HV
authors.lastname: Aposhian
mesh_terms: D000251:Adenosine Triphosphatases / Q000302:isolation & purification / Q000378:metabolism*; D001149:Arsenates / Q000378:metabolism*; D001152:Arsenicals / Q000378:metabolism; D053501:Arsenite Transporting ATPases; D018053:Arsenites / Q000378:metabolism*; D002250:Carbon Radioisotopes; D004229:Dithiothreitol / Q000494:pharmacology; D004795:Enzyme Stability; D006358:Hot Temperature; D006801:Humans; D016623:Ion Pumps; D007700:Kinetics; D016014:Linear Models; D008099:Liver / Q000201:enzymology*; D008297:Male; D008970:Molecular Weight; D009097:Multienzyme Complexes; D010084:Oxidation-Reduction; D013379:Substrate Specificity
chemical_list: D001149:Arsenates; D001152:Arsenicals; D018053:Arsenites; D002250:Carbon Radioisotopes; D016623:Ion Pumps; D009097:Multienzyme Complexes; D000251:Adenosine Triphosphatases; D053501:Arsenite Transporting ATPases; C020300:monomethylarsonic acid; C015001:arsenite; C025657:arsenic acid; D004229:Dithiothreitol