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The importance of being thiomethylated: formation, fate, and effects of methylated thioarsenicals
Citation:
Wang, Q., D. Thomas, AND H. Naranmandura. The importance of being thiomethylated: formation, fate, and effects of methylated thioarsenicals. CHEMICAL RESEARCH IN TOXICOLOGY. American Chemical Society, Washington, DC, , 281-289, (2015).
Impact/Purpose:
This manuscript provides a summary of current research on a topic relevant to continuing efforts to assess risk associated with chronic exposure to arsenic in water, air, soil, and food. This information should be of value in current efforts to assess aggregate exposure to this metalloid.
Description:
AbstractAlthough inorganic arsenic has long been recognized as a potent toxicant and carcinogen in humans, recent evidence shows that at least some of its effects are mediated by methylated metabolites. Elucidating the conversion of inorganic arsenic to mono-, di-, and tri-methylated species has provided insights into the enzymology of this pathway and identified genetic and environmental factors that influence the susceptibility of individuals to this metalloid's adverse health effects. Notably, almost all work on the formation, fate, and effects of methylated arsenicals has focused on oxoarsenicals in which arsenic is bound to one or more oxygen atoms. However, thioarsenicals are a class of arsenicals in which a sulfur atom has replaced one or more oxygens that is bound to arsenic. Thioarsenicals have been identified as urinary metabolites in humans and other animals following exposure to inorganic arsenic. Studies find that methylated thioarsenicals exhibit kinetic behavior and toxicological properties that distinguish them from methylated oxoarsenicals. This perspective considers that formation, fate, and effects of methylated thioarsenicals with an emphasis on examining the linkages between the molecular processes that underlie both methylation and thiolation reactions. Integrating this information will provide a more comprehensive view of the relationbetween metabolism of arsenic and the risk posed by chronic exposure to this environmental contaminant.
