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METABOLISM AS A DETERMINING FACTOR IN ACUTE AND CHRONIC TOXICITY OF INORGANIC ARSENIC
Citation:
STYBLO, M. AND D. J. THOMAS. METABOLISM AS A DETERMINING FACTOR IN ACUTE AND CHRONIC TOXICITY OF INORGANIC ARSENIC. Presented at Pittsburg Conference (Pittcon), Chicago, IL, February 25 - March 01, 2007.
Description:
The metabolism of inorganic arsenic (iAs) in humans involves reduction of As(V)-species to trivalency and oxidative methylation of As(III)-species. In this pathway, iAs is converted to methylarsenic (MAs) and dimethyl arsenic (DMAs) metabolites that contain As(III) or As(V). Recent reports show that one enzyme, arsenic (+3 oxidation state) methyltransferase (AS3MT), catalyzes all key steps in iAs metabolism. AS3MT is an S-adenosylmethionine-dependent enzyme and requires endogenous reductants for full activity (Fig. 1). AS3MT is expressed and active in primary human hepatocytes. AS3MT polymorphisms have been linked to specific patterns of iAs methylation, suggesting that mutations in AS3MT may be in part responsible for interindividual variability in iAs metabolism and possibly for differences among individuals in susceptibility to the adverse effects of iAs exposure.