How is Inorganic Arsenic Detoxified

Publisher Summary Arsenate is reduced to arsenite enzymatically by arsenate reductase and nonenzymatically by GSH. An early step in the detoxification appears to be the formation of the Gailer compound, seleno-bis(S-glutathionyl) arsinium ion, which is rapidly formed and excreted in the bile. Arsenite-binding proteins initially may prevent or enhance the accumulation of toxic levels of arsenite. As these binding sites become saturated, the arsenite may be released for methylation, a biotransformation process that results in the increase of urinary arsenic (As). Methylation of As species can occur via SAM and methyltransferases and/or nonenzymatically with methylvitamin B 12 , GSH, and selenite. Methylation by the methylvitamin B 12 system has been shown in vitro only. The substrate for DMA production appears to be MMA III . The lack of methyltransferases in many primates strongly indicates that methylation may not be the primary detoxification pathway for Asi. In fact, the environmental protection agency classifies dimethylarsinic acid, the final urinary metabolite for As in humans, as a probable human carcinogen. The determination of the amino acid sequences of the As methyltransferases needs to be accomplished so that gene probes can be constructed to better study As methyltransferase polymorphism, as it is related to the various responses of people to Asi.