Biomethylation Mechanisms

Biomethylation is the preferred detoxification mechanism for inorganic arsenicals. 

Fig. 7. Challenger mechanism for biomethylation of arsenic. Solid arrows represent pathways proposed originally dashed arrows represent additional pathways proposed by the present authors.

Fig. 8. Proposed mechanism for the biomethylation of selenium. Adapted from Reamer and Zoller (106). Copyright 1980 by the American Association for the Advancement of Science. Dashed arrows represent pathways proposed by the present authors.

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). 

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. 

Cadmium shows a very high bioconcentration factor (BCF), mainly because of its extremely slow elimination, although the absorption is rather low. The metal is not biomethylated and does not exist in any highly bioavailable organic forms. Its uptake is coupled to calcium and iron transporting mechanisms in which cadmium is mistaken for the essential metal and consequently transported. The uptake of cadmium is thus enhanced in situations of iron deficiency. 

Oxidation of sulfur entities of metal sulfides to obtain energy is an example of direct dissolving action under aerobic conditions (Kurek, 2002). When oxidized metal compounds [e.g., Fe(III), Mn(IV), As(V)] act as electron acceptors, anaerobic respiration becomes an example of direct dissolving action under anaerobic conditions (Ahmann et al., 1994 Ehrlich, 2002). Volatilization of metals and metalloids or biomethylated metals and metalloid compounds from the soil into the atmosphere can be a mechanism of detoxification of toxic elements such as Hg, As, and Se for microorganisms (Gadd, 1993). 

The extent of these potential methylation mechanisms in nature remains uncertain, as is the degree to which anthropogenic release of these potential methylating agents influences methylation in the environment. Controversy still exists over the occurrence of direct biomethylation of certain metals, such as Pb in nature. 

During the course of biomethylation the methyl group is most likely transferred as a bridging intermediate rather than a free entity. Such an intermediate is assumed to form during an associative mechanism [4]. The methyl group may be electrophilic (cationic), radical or nucleophilic (anionic), depending on the specific donor moiety. A broad variety of methyl transfer reactions are therefore possible. Besides the two biological donors, methylcobalamin (see below) and S-adenosyl-methonine (1) nonenzymatic transmethylation is also possible in the natural environment, probably also very important for the formation and decomposition of metal methyl compounds [3b],... 

Tellurium biomethylation also occurs via the Challenger mechanism. However, it is not yet clear whether or not the same enzymes are used as in the case of sele-... 

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