Biological Transmethylation Rate Studies

Systems where in vivo methylation is the principal step are not as readily susceptible to quantitative measurements as the chemical systems just discussed. Various obstacles remain to be overcome in order to develop a complete picture of such in vivo processes. These are as follows  

For various reasons, and especially the Minamata disaster, most kinetic studies on in vivo transmethylation have concentrated on mercury. The great majority of these have involved individual species of microorganisms or microbial communities as the actual methylators. There have been several reviews on the role of microorganisms in transmethylation (5, 6, 72) and other cyclic processes involving metals or metalloids (25, 73-75). 

After a long fallow period, other workers have recently begun to extend Challenger s arsenic biomethylation work (1-3). Cox and Alexander have studied this reaction by the mold Candida humicola (59-9/). The overall reaction may be summed up by the reaction shown in Eq. (6). Both cell extracts and whole cells of Methanobacterium strain M.o.H. converted arsenate to dimethylarsine (92). Investigations on C. humicola and other molds determined that the rate of (CH s production follows the growth rate pattern of the mold, and decreases when the mold reaches the resting phase (93). The methylated arsenic intermediates were identified by use of 

74As-labeled starting materials (94). WhenC. humicola was preconditioned by treatment with cacodylate ion, the rate of subsequent trimethylarsine production from arsenate or cacodylate increased, possibly due to a permanent As build-up in cell walls (95). 

Human volunteers who drank wine containing inorganic arsenic excreted methylarsonic and cacodylic acids in their urine (96). These two compounds also occur in the urine of copper smelters, the elevated arsenic content presumably coming from copper ores (97). Cacodylate ion forms when H34As04 is administered orally to dogs or hamsters (98-100). A Japanese group reported that various small animals will form methylar-sonate and cacodylate from H3ASO4 (101). On the basis of presently available data, it remains uncertain whether arsenic biomethylation occurs from the bodily processes of the mammals themselves or from microflora of the intestinal tract. 

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