A review of the enzymology of arsenic metabolism and a new potential role of hydrogen peroxide in the detoxication of the trivalent arsenic species.
This laboratory has studied the enzymology involved in the biotransformation of inorganic arsenic to dimethylarsinous acid (DMA(III)) and in human studies established that monomethylarsonous acid (MMA(III)) and DMA(III) appear in urine of people chronically exposed to arsenic. It appears that only two proteins are required for inorganic arsenic biotransformation in the human, namely, monomethylarsonic acid (MMA(V)) reductase and arsenic methyltransferase. MMA(V) reductase and the unique glutathione transferase omega (hGST-O) are identical proteins. Arsenicals with a +3 oxidation state are more toxic than the +5 species. While methylation of arsenite, MMA(III), and DMA(III) produces less toxic +5 oxidation arsenic species containing an additional methyl group such as MMA(V), dimethylarsinic acid (DMA(V)), and TMAO, a new mechanism involving hydrogen peroxide for detoxifying arsenite, MMA(III), and DMA(III) is proposed based on in vitro experiments.
Aposhian
H Vasken
HV
Department of Molecular and Cellular Biology, The University of Arizona, Tucson, AZ 85721-0106, USA. aposhian@u.arizona.edu
Zakharyan
Robert A
RA
Avram
Mihaela D
MD
Sampayo-Reyes
Adriana
A
Wollenberg
Michael L
ML
D000818:Animals; D001151:Arsenic / Q000378:metabolism / Q000493:pharmacokinetics; D001152:Arsenicals / Q000378:metabolism*; D001711:Biotransformation; D002101:Cacodylic Acid / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008658:Inactivation, Metabolic; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008745:Methylation
D001152:Arsenicals; D002101:Cacodylic Acid; D006861:Hydrogen Peroxide; C020300:monomethylarsonic acid; D001151:Arsenic