Methylation of arsenic

FIGURE 8.6 Methylation of arsenate (after Environmental Health Criteria 18). 

Conversion of a nontoxic molecule to one that is toxic, or a molecule with low potency to one that is more potent. Examples include the formation of the phenoxy herbicide 2,4-D from the corresponding butyrate, formation of nitrosamines, and methylation of arsenicals to trimethylarsine. 

Aposhian, H.V., R. Zakharyan, Y. Wu, S. Healy, and M.M. Aposhian. 1997. Enzymatic methylation of arsenic compounds. II. An overview. Pages 296-321 in C.O. Abernathy, R.L. Calderon, and W.R. Chappel (eds.). Arsenic. Exposure and Health Effects. Chapman Hall, London. 

Arsenic causes both skin and lung cancer. Skin cancer was observed over 100 years ago in patients treated with arsenical compounds, and lung cancer was seen in smelter workers who chronically inhaled arsenic dust. Although arsenic is an established human carcinogen, it has been difficult to confirm and study in animal models. Arsenic readily crosses the placenta, but there appears to be increased methylation of arsenic to its organic form, which reduces its toxicity to the fetus. 

Bacterial methylation of arsenate by a methanogen was first reported by McBride and Wolfe (135) in 1971, and reports of nonmethanogenic bacterial methylation followed. These transformations are now known to be effected by a range of bacteria, and the mechanisms are likely to be similar to those proposed for fungi (32). 

Methylation of arsenic is an important pollution problem because of the widespread use of arsenic compounds in insecticides and because of the presence of arsenate in the phosphate used in household detergents.421 422 After reduction to arsenite, methylation occurs in two steps (Eq. 16-45). Additional reduction steps result in the formation of dimethylarsine, one of the principal products of action of methanogenic bacteria on arsenate. The methyl transfer is shown as occurring through CH3+, with an accompanying loss of a proton from the substrate. However, a CH3 radical may be transferred with formation of a cobalt(II) corrinoid.423... 

The methylation of arsenic is entirely or almost entirely biotic (Frankenberger and Arshad, 2002), 367. Specifically, certain fungi (including yeasts) and bacteria are capable of methylating arsenic ((Bentley and Chasteen, 2002), 257-260 (Cullen and Reimer, 1989), 717-724 Chapter 4). Only limited evidence exists for the chemical (abiotic) methylation of arsenic. As mentioned earlier, some volatile arsines have been produced in the laboratory from photochemical reactions involving As(III), carboxylic acids, and ultraviolet radiation (Guo et al., 2005 McSheehy et al., 2005). 

In the Challenger mechanism or scheme, oxidative methylation of arsenicals containing As(III) produces a methylated product that contains As(V). Because methylation is oxidative, As(V) must be reduced to trivalency before it can be methylated. Hence, the pathway for the formation of mono-, di-, and trimethylated arsenic species consists of alternating oxidation and reduction reactions (Chapter 2). 

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). 

Wildfang, E., Zakharyan, R.A. and Aposhian, H.V. (1998) Enzymatic methylation of arsenic compounds VI. Characterization of hamster liver arsenite and methylarsonic acid methyltransferase activities in vitro. Toxicology and Applied Pharmacology, 152(2), 366-75. 

Zakharyan, R.A., Ayala-Fierro, F., Cullen, W.R. et al. (1999) Enzymatic methylation of arsenic compounds. VII. Monomethylarsonous acid (MMA(III)) is the substrate for MMA methyltransferase of rabbit liver and human hepatocytes. Toxicology and Applied Pharmacology, 158(1), 9-15. 

Zakharyan, R., Wu, Y., Bogdan, G.M. and Aposhian, H.V. (1995) Enzymatic methylation of arsenic compounds Assay, partial purification, and properties of arsenite methyltransferase and monomethylarsonic acid methyltransferase of rabbit liver. Chemical Research in Toxicology, 8(8), 1029-38. 

Biological methylation of arsenic is effected via the transfer of a carbocation, a process known as oxidative... 

Aposhian, H.V. (1997). Enzymatic methylation of arsenic species and other new approaches to arsenic toxicity. Anna. Rev. Pharmacol. Toxicol. 31 397-419. 

Examples of the Influence of Adsorption on Kinetics. Three cases of arsenic species transformations influenced by adsorption are considered in this section. The three cases considered are 1) reactant not adsorbed, product adsorbed (e.g. demethylation of cacodylic acid to arsenate), 2) reactant adsorbed, product not adsorbed (e.g. methylation of arsenate to cacodylic acid),... 

Demethylation of cacodylic acid to arsenate was chosen as an example of case 1, product adsorbing with reactant not adsorbing, because cacodylic acid is only weakly adsorbed by anaerobic sediments and arsenate is strongly adsorbed. For the same reason, methylation of arsenate to produce cacodylic acid was chosen as an example of case 2, reactant adsorbed and product not adsorbed. Demethylation of methanearsonic acid to arsenate was chosen as an example of case 3, reactant and product both adsorbing. 

Predicted arsenate and cacodylic acid vs time curves for methylation of arsenate to produce cacoi ylic acid are plotted in Figures 6 and 7, respectively. Adsorption of arsenate lowers the dissolved arsenate concentration and, therefore, results in a slower rate of methylation. The... 

Figure 7. Dissolved cacodijlic acid concentration from methylation of arsenate, (a)U = 0 (b)U = 60gLK...

P. T. S. Wong, Y. K. Chau, L. Luton, G. A. Bengut and D. J. Swaine, Methylation of Arsenic in the Aquatic Environment, Conference Proceedings on Trace Substances in Environmental Health, XI, Hemphill, University of Missouri, U.A.A., 1977. 

The mechanisms of biomethylation of arsenic have not been documented. However, Cullen and coworkers have proposed a plausible mechanistic model based on oxidative methylation of arsenic(III) by S-adenosylmethionine and reduction by a thiol such as lipoic acid. 

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