In vitro methylation of arsenite by rabbit liver cytosol: Effect of metal ions, metal chelating agents, methyltransferase inhibitors and uremic toxins

The methylation of carrier-free As-74-arsenite by liver cytosol of Flemish Giant rabbits is highly susceptible to additions of trace elements. In vitro supplementation of essential trace elements like zinc (Zn2+), vanadium (V5+), iron (Fe2+) copper (Cu2+) and selenate was shown to increase the methylation efficiency. Trivalent metal ions (e.g. Al3+, Cr3+ and Fe3+), Hg2+, Tl+ and SeO32- had a deleterious effect The inhibitory effect of EDTA, oxime and many divalent cations (Ca2+,Mg2+, Sr2+,...) suggest a co-factor role for a specific divalent metal ion, possibly Zn2+. Chelating agents used in clinical treatment of acute and chronic inorganic arsenic poisoning lower the methylation capacity of cytosol by rendering the trivalent arsenic unavailable for the methyltransferase enzymes. S-adenosylhomocysteine and periodate-oxidized adenosine, inhibitors of s-adenosylmethionine dependent methylation pathways, inhibit the methylation of arsenite. Pyrogallol, a catechol-O-methyltransferase inhibitor, blocks the action of arsenite- and monomethylarsonic methyltransferase enzymes, suggesting a close structural relationship between the active sites of the different enzymes. Some uraemic toxins, namely oxalate, p-cresol hypoxanthine, homocysteine and myo-inositol, inhibit arsenic methylation.