砷代谢酶学综述以及过氧化氢在三价砷解毒中的新潜在作用。

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

作者信息

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

机构信息

Department of Molecular and Cellular Biology, The University of Arizona, Tucson, AZ 85721-0106, USA.

出版信息

Toxicol Appl Pharmacol. 2004 Aug 1;198(3):327-35. doi: 10.1016/j.taap.2003.10.027.

DOI:10.1016/j.taap.2003.10.027

PMID:15276412

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.

摘要

本实验室研究了无机砷生物转化为二甲基胂酸（DMA(III)）所涉及的酶学，并通过人体研究确定，长期接触砷的人群尿液中会出现一甲基胂酸（MMA(III)）和DMA(III)。看来人体中无机砷生物转化仅需两种蛋白质，即一甲基胂酸（MMA(V)）还原酶和砷甲基转移酶。MMA(V)还原酶与独特的谷胱甘肽转移酶ω（hGST-O）是同一蛋白质。氧化态为+3的砷化合物比+5价的毒性更强。虽然亚砷酸盐、MMA(III)和DMA(III)甲基化会产生毒性较小的含额外甲基的+5氧化态砷化合物，如MMA(V)、二甲基胂酸（DMA(V)）和氧化三甲胺，但基于体外实验提出了一种涉及过氧化氢的新机制，用于亚砷酸盐、MMA(III)和DMA(III)的解毒。