Arsenite methylation by methylvitamin B12 and glutathione does not require an enzyme

• Published in: Toxicology and applied pharmacology Vol. 154; no. 3; pp. 287 - 291
• Main Authors: ZAKHARYAN, R. A, APOSHIAN, H. V
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier 01-02-1999
• Subjects: Arsenicals - metabolism; Arsenites - metabolism; Biological and medical sciences; Cacodylic Acid - metabolism; Chemical and industrial products toxicology. Toxic occupational diseases; Cytosol - metabolism; Drug Synergism; Enzymes - metabolism; Glutathione - pharmacology; Humans; Liver - metabolism; Medical sciences; Metals and various inorganic compounds; Methylation - drug effects; Reducing Agents - pharmacology; Sodium Selenite - pharmacology; Teratogens - metabolism; Toxicology; Unithiol - pharmacology; Vitamin B 12 - analogs & derivatives; Vitamin B 12 - pharmacology; Human; Arsenic; Liver; Metabolic activation; Metabolism; Methylation; Cytosol; In vitro; Cyanocobalamin; Arsenites; Glutathione; Mecobalamin
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1006/taap.1998.8587

Although inorganic arsenic is methylated enzymatically by arsenic methyltransferases, which have been found in many mammalian livers, the detection of such enzymes has not been successful in surgically removed human livers. Results of the present experiments demonstrated that methylvitamin B12 (methylcobalamin, CH3B12) in the presence of thiols and inorganic arsenite can produce, in vitro, substantial amounts of monomethylarsonic acid (MMA) and small amounts of dimethylarsinic acid (DMA) in the absence of enzymes. Furthermore, this nonenzymatic methylation of inorganic arsenite by CH3B12 was increased substantially by the presence of dimercaptopropanesulfonate (DMPS) and/or sodium selenite. The actions of DMPS and selenite together were additive. The methylation by CH3B12 was neither inhibited nor stimulated by human liver cytosol. Since the amount of MMA produced by the in vitro system described in this study was not small, these results emphasize the need for a properly designed nutritional study in humans exposed to inorganic arsenic as to the relationship between vitamin B12, selenium, and the metabolism of carcinogenic inorganic arsenic.