Metabolism of the carcinogen chromate by cellular constituents
Metabolism of the carcinogen chromate by cellular constituents
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DOI：
10.1007/bfb0111319
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
P. Connett;K. Wetterhahn
中科院分区：
文献类型：
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作者：
P. Connett;K. Wetterhahn
铬（VI）的氧化还原化学相对于致癌物质铬酸盐在体内的细胞代谢进行了讨论。被认为是细胞还原铬（VI）的铬（III）的可能的网站。本文介绍了在生理条件下氨基酸、抗坏血酸、羧酸、巯基分子及其它小分子与铬酸根的反应。一般来说，只有抗坏血酸盐和那些含有巯基的分子能够在pH 7.4下容易地还原铬酸盐。因此，在细胞质中，谷胱甘肽、半胱氨酸和抗坏血酸可能与铬酸盐反应。虽然大多数蛋白质对铬酸盐无反应性，但某些氧化还原蛋白质在还原铬酸盐中具有活性。血红素蛋白血红蛋白和细胞色素P-450具有铬酸盐还原酶活性，而细胞色素c和肌红蛋白是无活性的。NADPH依赖性黄素酶谷胱甘肽还原酶和NADPH-细胞色素P-450还原酶也具有铬还原酶活性。然而，NAD（P）H酶、异柠檬酸脱氢酶、谷氨酸脱氢酶和苹果酸脱氢酶不还原铬酸盐。微粒体和线粒体都具有铬还原酶活性。微粒体活性由NADPH-细胞色素P-450还原酶/细胞色素P-450系统负责。负责线粒体还原铬酸盐的酶尚未鉴定。铬（VI）及其代谢物铬（III）抑制结合铬（III）或还原铬酸盐的酶的正常活性。铬酸盐的代谢涉及反应性中间体的产生，其最终与细胞成分结合并损害它们在细胞中的功能。
The redox chemistry of chromium(VI) is discussed with respect to the cellular metabolism of the carcinogen chromate in vivo. Possible sites for cellular reduction of chromium(VI) to chromium(III) are considered. The reactions of amino acids, ascorbic acid, carboxylic acids, thiol-containing mole-cules and other small molecules with chromate under physiological conditions are presented. In general only ascorbate and those molecules containing sulfhydryl groups are capable of easily reducing chromate at pH 7.4. Thus, in the cytoplasm, glutathione, cysteine and ascorbate are likely candidates to react with chromate. While most proteins are unreactive toward chromate, certain redox proteins are active in reducing chromate. The heme proteins hemoglobin and cytochrome P-450 possess chromate-reductase activity, whereas cytochrome c and myoglobin are inactive. The NADPH-dependent flavoenzymes glutathione reductase and NADPH-cytochrome P-450 reductase also possess chromate-reductase activity. However, the NAD(P)H enzymes, isocitrate dehydrogenase, glutamate dehyrogenase and malate dehydrogenase do not reduce chromate. Both microsomes and mitochondria possess chromate-reductase activity. The microsomal activity is accounted for by the NADPH-cytochrome P-450 reductase/cytochrome P-450 system. The enzyme(s) responsible for the mitochondrial reduction of chromate have not been identified. Chromium(VI) and its metabolite chromium(III) inhibit the normal activities of enzymes which bind chromium(III) or reduce chromate. The metabolism of chromate involves the generation of reactive intermediates which ultimately bind to cellular constituents and damage their function in the cell.