A review of the enzymology of arsenic metabolism and a new potential role of hydrogen peroxide in the detoxication of the trivalent arsenic species

H. Vasken Aposhian, Robert A. Zakharyan, Mihaela D. Avram, Adriana Sampayo-Reyes, Michael L. Wollenberg

Research output: Contribution to journalReview articlepeer-review

182 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)327-335
Number of pages9
JournalToxicology and Applied Pharmacology
Volume198
Issue number3
DOIs
StatePublished - Aug 1 2004
Externally publishedYes

Keywords

  • Arsenic
  • Detoxication
  • DMA
  • generic term including DMA and DMA
  • generic term including MMA and MMA
  • Hydrogen peroxide
  • MMA
  • MMA
  • MMA
  • monomethylarsonic acid
  • monomethylarsonous acid

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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