Inorganic arsenic metabolic methylation process

Most of the inorganic arsenic is metabolized in the body to methylated arsenic species. Methylation of arsenic involves a stepwise process of two-electron reduction of the pentavalent arsenic species [e.g., As(V), MMA(V), and DMA(V)] to the trivalent arsenic species [e.g., As(III), MMA(III), and DMA(III)], followed by oxidative addition of a methyl group to the trivalent arsenic (Scheme 1) (5,88). Glutathione, cysteine, and dithiothreitol can act as reducing agents, and S-adenosylmethionine (SAM) is the methyl donor. Dimeth-ylarsinous acid (V) [DMA(V)] is the usual end product detected in humans. Tri-methylarsine oxide (V) [TMAO(V)] and trimethylarsine (III) [TMA(III)] are the end products produced by some microorganisms TMAO(V) is also produced by rats and mice. 

As is the case with isotopic labeling of molecules, enriched levels of stable isotopes of elements can be used as tracers. Isotopes of elements can be used as nutritional supplements for plants or animals to trace absorption, assimilation, and metabolism of elements (Allen and Georgitis). Processes such as biomethylation of elements like mercury and arsenic in the environment can be studied using isotopically enriched elements. In some cases, methylated metals are more toxic than the inorganic species, and generally accumulate up the food chain. 

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