TY - JOUR
T1 - A review of the enzymology of arsenic metabolism and a new potential role of hydrogen peroxide in the detoxication of the trivalent arsenic species
AU - Vasken Aposhian, H.
AU - Zakharyan, Robert A.
AU - Avram, Mihaela D.
AU - Sampayo-Reyes, Adriana
AU - Wollenberg, Michael L.
N1 - Funding Information:
This work was supported in part by the Superfund Basic Research Program NIEHS Grant Number ES-04940 from the National Institute of Environmental Health Sciences and the Southwest Environmental Health Sciences Center P30-ES-06694.
PY - 2004/8/1
Y1 - 2004/8/1
N2 - 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.
AB - 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.
KW - Arsenic
KW - DMA
KW - Detoxication
KW - Hydrogen peroxide
KW - MMA
KW - MMA
KW - MMA
KW - generic term including DMA and DMA
KW - generic term including MMA and MMA
KW - monomethylarsonic acid
KW - monomethylarsonous acid
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U2 - 10.1016/j.taap.2003.10.027
DO - 10.1016/j.taap.2003.10.027
M3 - Review article
C2 - 15276412
AN - SCOPUS:3242801408
SN - 0041-008X
VL - 198
SP - 327
EP - 335
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 3
ER -