Elucidating the pathway for arsenic methylation

11-Jan-2018 08:44

Although phosphate and arsenate are structurally similar, there is no evidence that arsenic replaces phosphorus in DNA or RNA.Anthropogenic (man-made) sources of arsenic, like the natural sources, are mainly arsenic oxides and the associated anions.Studies in experimental animals and humans show that both inorganic arsenic and methylated metabolites cross the placenta to the fetus, however, there is evidence that methylation is increased during pregnancy and that it could be highly protective for the developing organism.Enzymatic methylation of arsenic is a detoxification process; it can be mehylated to methylarsenite, dimethylarsenite or trimethylarsenite, all of which are trivalent.The catalysis involves thiolates of Cys72, Cys174, and Cys224.In an SN2 reaction, the positive charge on the SAM sulfur atom pulls the bonding electron from the carbon of the methyl group, which interacts with the arsenic lone pair to form an As−C bond, leaving SAH.Despite, or possibly because of, its long-known toxicity, arsenic-containing potions and drugs have a history in medicine and quackery that continues into the 21st century.Starting in the early 19th century and continuing into the 20th century, Fowler's solution, a toxic concoction of sodium arsenite, was sold.

For example, many ores, especially sulfide minerals, are contaminated with arsenic, which is released in roasting (burning in air).The main metabolites excreted in the urine of humans exposed to inorganic arsenic are mono- and dimethylated arsenic acids, together with some unmetabolized inorganic arsenic.With the uptake of arsenic within cells and the subsequent reactions that result in the production of reactive oxygen species (ROS), the Nrf2 unbinds and becomes active.In combination with all-trans retinoic acid, it is FDA-approved as first-line treatment for promyelocytic leukemia.

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Inorganic arsenic and its compounds, upon entering the food chain, are progressively metabolised (detoxified) through a process of methylation.The related drug Melarsoprol is still in use against late-state African trypanosomiasis (sleeping sickness), despite its high toxicity and possibly fatal side effects.Arsenic trioxide (As which are normally immortal and can multiply without limit.In such processing, arsenide is converted to arsenic trioxide, which is volatile at high temperatures and is released into the atmosphere.

Oct 28, 2014. Our previous work evaluating iAs3+ methylation catalyzed by recombinant human arsenic III methyltransferase hAS3MT suggested that the valence state of arsenic was not changed in the transmethylation 16. Thomas DJ, Waters SB, Styblo M 2004 Elucidating the pathway for arsenic methylation.… continue reading »

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Elucidating the pathway of inorganic arsenic metabolism shows that some of methylated arsenicals formed as intermediates and products are reactive and toxic species. Hence, methylated arsenicals likely mediate at least some of the toxic and carcinogenic effects associated with exposure to arsenic. Trimethylarsonium.… continue reading »

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To further investigate the partially understood phenomena relating to arsenic toxicity and the uses of arsenic as a drug, it is important to elucidate the exact pathways involved in metabolism of this metalloid, as the toxicity and the clinical uses of arsenic can be best recognized in context of its biotransformation. Thereby, in.… continue reading »

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Abstract. To elucidate the influence of folate concentration on the association between urinary arsenic profiles and urothelial carcinoma UC. lation of MMAV by an increased upstream input and a reduced downstream output of the arsenic methylation pathway metabolites. In addition to bladder cancer, our previous.… continue reading »

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