Reduction of mitomycin C is catalysed by human recombinant NRH:quinone oxidoreductase 2 using reduced nicotinamide adenine dinucleotide as an electron donating co-factor
Reduction of mitomycin C is catalysed by human recombinant NRH:quinone oxidoreductase 2 using reduced nicotinamide adenine dinucleotide as an electron donating co-factor
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DOI：
10.1038/sj.bjc.6603414
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发表时间：
2006-11-06
影响因子：
8.8
通讯作者：
Boddy, A. V.
中科院分区：
文献类型：
--
作者：
Jamieson, D.;Tung, A. T. Y.;Boddy, A. V.
NRH：醌氧化还原酶2（NQO2）已被描述为与烟酰胺腺嘌呤二核苷酸（NADH）或NADPH作为供电子共底物没有酶活性。丝裂霉素C（MMC）是NQO2同系物NQO1的底物和机制抑制剂。NRH：醌氧化还原酶2在pH 5.8下以NADH作为辅因子催化MMC的还原。该反应产生抑制NQO2介导的CB 1954代谢的物质。此外，MMC导致转染过表达NQO2的细胞系中DNA交联的增加，其程度与用等基因NQO1表达细胞系观察到的程度相当。这些数据表明，NQO2可能有助于MMC代谢为细胞毒性物质。
NRH:Quinone Oxidoreductase 2 (NQO2) has been described as having no enzymatic activity with nicotinamide adenine dinucleotide (NADH) or NADPH as electron donating cosubstrates. Mitomycin C (MMC) is both a substrate for and a mechanistic inhibitor of the NQO2 homologue NQO1. NRH:quinone oxidoreductase 2 catalysed the reduction of MMC at pH 5.8 with NADH as a co-factor. This reaction results in species that inhibit the NQO2-mediated metabolism of CB1954. In addition, MMC caused an increase in DNA cross-links in a cell line transfected to overexpress NQO2 to an extent comparable to that observed with an isogenic NQO1-expressing cell line. These data indicate that NQO2 may contribute to the metabolism of MMC to cytotoxic species.