Mechanisms of arsenic biotransformation
Mechanisms of arsenic biotransformation
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DOI：
10.1016/s0300-483x(02)00285-8
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发表时间：
2002-12-27
期刊：
影响因子：
4.5
通讯作者：
Vahter, M
中科院分区：
文献类型：
--
作者：
Vahter, M
无机砷是一种有文献记载的人类致癌物，在体内通过将五价砷还原为三价和从S-腺苷甲硫氨酸中加入甲基而甲基化。谷氨酸和可能的其他硫醇充当还原剂。肝脏是砷甲基化最重要的部位，但大多数器官显示砷甲基化活性。最终代谢产物为甲基胂酸（MMA）和二甲基胂酸（DMA）。与无机砷相比，砷与组织成分的反应性较低，并容易随尿排出。然而，可形成反应性中间体。吸收的砷酸盐（As-V）在血液中相当迅速地还原为As-III，这意味着毒性增加。此外，在人尿液中检测到甲基化代谢物MMA（III）和DMA（III）的中间还原形式。特别是MMA（III）具有高毒性。MMA（III）和DMA（III）在多大程度上有助于观察到的毒性暴露于无机砷仍有待阐明。砷的代谢在哺乳动物种属、种群和个体之间存在显著差异。有迹象表明，与尿中MMA含量较高的受试者相比，尿中MMA含量较低的受试者对摄入的砷的消除速度更快。(C)2002年由Elsevier Science爱尔兰有限公司出版。
Inorganic arsenic, a documented human carcinogen, is methylated in the body by alternating reduction of pentavalent arsenic to trivalent and addition of a methyl group from S-adenosylmethionine. Glutathione, and possibly other thiols, serve as reducing agents. The liver is the most important site of arsenic methylation, but most organs show arsenic methylating activity. The end metabolites are methylarsonic acid (MMA) and dimethylarsinic acid (DMA). These are less reactive with tissue constituents than inorganic arsenic and readily excreted in the urine. However, reactive intermediates may be formed. Absorbed arsenate (As-V) is fairly rapidly reduced in blood to As-III, which implies increased toxicity. Also, intermediate reduced forms of the methylated metabolites, MMA(III) and DMA(III), have been detected in human urine. In particular MMA(III) is highly toxic. To what extent MMA(III) and DMA(III) contribute to the observed toxicity following exposure to inorganic arsenic remains to be elucidated. There are marked differences in the metabolism of arsenic between mammalian species, population groups and individuals. There are indications that subjects with low MMA in urine have faster elimination of ingested arsenic, compared to those with more MMA in urine. (C) 2002 Published by Elsevier Science Ireland Ltd.