NADPH细胞色素P-450还原酶将醌类抗癌剂激活为自由基。
NADPH cytochrome P-450 reductase activation of quinone anticancer agents to free radicals.
作者信息
Bachur N R, Gordon S L, Gee M V, Kon H
出版信息
Proc Natl Acad Sci U S A. 1979 Feb;76(2):954-7. doi: 10.1073/pnas.76.2.954.
Abstract
With NADPH as the electron donor, rat liver NADPH cytochrome P-450 reductase (NADPH:ferricytochrome oxidoreductase, EC 1.6.2.4) catalyzes the single-electron reduction of several quinone antibiotics to a semiquinone or free radical state. The benzanthraquinones adriamycin, daunorubicin, carminomycin, 7-O-methylnogalarol, and aclacinomycin A and the N-heterocyclic quinones streptonigrin and mitomycin C are activated to free radical intermediates which can transfer their single electron to molecular oxygen to form superoxide. The overall Km range for this electron transfer is 0.4 to 42.1 X 10(-4) M. We postulate that the formation of the "site-specific free radical/ intermediate is central to the cytotoxic action of these antibiotics.
摘要
以还原型辅酶Ⅱ（NADPH）作为电子供体，大鼠肝脏NADPH细胞色素P-450还原酶（NADPH：铁细胞色素氧化还原酶，EC 1.6.2.4）催化几种醌类抗生素单电子还原为半醌或自由基状态。苯并蒽醌类的阿霉素、柔红霉素、洋红霉素、7-O-甲基诺加罗醇、阿克拉霉素A以及N-杂环醌类的链黑菌素和丝裂霉素C被激活形成自由基中间体，这些中间体可将其单电子转移给分子氧形成超氧化物。这种电子转移的总体米氏常数（Km）范围为0.4至42.1×10⁻⁴ M。我们推测“位点特异性自由基/中间体的形成是这些抗生素细胞毒性作用的核心”。
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