Arsenic, methylation

Management of chronic arsenic poisoning consists primarily of termination of exposure and nonspecific supportive care. Although empiric short-term oral chelation with unithiol or succimer for symptomatic individuals with elevated urine arsenic concentrations may be considered, it has no proven benefit beyond removal from exposure alone. Preliminary studies suggest that dietary supplementation of folate—thought to be a cofactor in arsenic methylation—might be of value in arsenic-exposed individuals, particularly men, who are also deficient in folate. 

Subsequent work on the molecular basis of arsenic methylation can be divided into two areas based on the Challenger scheme, which posits the existence of two distinct processes in arsenic methylation. These are the reduction of As(V) to As(III) and the oxidative methylation of arsenicals containing As(III) to As(V). 

Buchet, J.P. and Lauwerys, R. (1985) Study of inorganic arsenic methylation by rat liver in vitro Relevance for the interpretation of observations in man. Archives of Toxicology, 57(2), 125-29. 

Drobna, Z., Xing, W., Thomas, D.J. and Styblo, M. (2006) shRNA silencing of AS3MT expression minimizes arsenic methylation capacity of HepG2 cells. Chemical Research in Toxicology, 19(7), 894-98. 

Li, J., Waters, S.B., Drobna, Z. et al. (2005) Arsenic (+3 oxidation state) methyl transferase and the inorganic arsenic methylation phenotype. Toxicology and Applied Pharmacology, 204(2), 164-69. 

Cullen et al. (1994) have proposed a possible mechanism of arsenic methylation after the study in which arsenite, arsenate, monomethyl-arsonate or dimethylarsinic acid were added to the growth medium in the presence of the unicellular alga Polyphsa peniculus. Evidence of arsenic biomethylation by the micro-organism Apiotrichum humicola in the presence of L-methionine-methyl-d3 has come from the same laboratory (Cullen et al., 1995). Their findings point to the role of S-adenosylmethionine, or a related sulfonium compound as possible methyl donors. Arsenic biomethylation and biotransformation has also been demonstrated in a freshwater environment (Kuroiwa et al., 1994). 

D.J. Thompson, A chemical hypothesis for arsenic methylation in mammals. Chem. Biol. Interact. 88 89, 1993. 

Studies of microbial systems have shown that the prodnc-tion of trimethylarsine from the various methylarsonates is more rapid than their respective thioarsinites, for example, Me2AsSR, MeAs(SR)2. However, there is a possible role for the thioarsinite in arsenic methylation. Studies on the binding of arsenic to the methyltransferase enzyme suggest that prior to the transfer of the methyl group the arsine oxide becomes bound to a thiolate at the active site. In this way it is possible to assist the binding of the softer arsenic substrate prior to... 

An X-ray diffraction study indicates that [Me2AsInMe2]3 contains two independent molecules per asymmetric unit in the solid state, one with a planar (Asln)3 ring while the other is puckered. However, a dynamic H NMR study indicates equivalence of the indium methyls and of the arsenic methyls in solution down to -80 °C. [(t-Bu)2AsInMe2]2 is dimeric by X-ray and mass spectral studies and the (Asln)2 core is planar. 

Gailer, J., Irgolic, K.J. The ion-chromatographic behavior of arsenite, arsenate, methyl-arsonic acid and dimethylarsinic acid on the hamilton PRP-XlOO anion-exchange column. Appl. Organomet. Chem. 8, 129-140 (1994)... 

Honschopp, S., Brunken, N., Nehrhom, A., Breunig, H.J. (1996). Isolation and characterization of a new arsenic methylating hacterium from soil. Microbiol. Res. 151 37-41. 

Islam, S.M., Fukushi, K., Yamamoto, K. (2005). Development of an enumeration method for arsenic methylating bacteria from mixed culture samples. Biotechnol. Lett. 27 1885-90. 

Gudzinowicz and Martin used the same method for quantitative studies of organoarsenic (triphenylarsine and trivinylarsine) and organobromo-arsenic (methyl, ethyl and butyl bromoarsines) compound mixtures. 

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