DT-DIAPHORASE AS A QUINONE REDUCTASE - A CELLULAR CONTROL DEVICE AGAINST SEMI-QUINONE AND SUPEROXIDE RADICAL FORMATION
DT-DIAPHORASE AS A QUINONE REDUCTASE - A CELLULAR CONTROL DEVICE AGAINST SEMI-QUINONE AND SUPEROXIDE RADICAL FORMATION
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DOI：
10.1016/0003-9861(82)90202-8
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发表时间：
1982-01-01
影响因子：
3.9
通讯作者：
ERNSTER, L
中科院分区：
文献类型：
--
作者：
LIND, C;HOCHSTEIN, P;ERNSTER, L
在 NADPH 存在下孵育的大鼠肝微粒体通过 2 种途径催化甲萘醌（2-甲基-1,4-萘醌）的氧化：NADPH-细胞色素 P-450 还原酶和 DT-心肌黄酶。前一种途径产生不稳定的半醌，如非化学计量的 NADPH 氧化和伴随的 O2 消耗所揭示的，半醌很容易自动氧化。另一方面，DT-心肌黄酶催化的甲萘醌还原产生相对稳定的对苯二酚，伴随着 NADPH 的化学计量氧化且不消耗 O2。给定量的甲萘醌氧化的 NADPH 总量反映了 2 种途径的相对贡献，这可以通过添加 2 种酶的选择性抑制剂或通过分别优先诱导 NADPH-细胞色素 P-450 还原酶和 DT-心肌黄酶的苯巴比妥或 3-甲基胆蒽处理大鼠来证明。添加含有大量细胞 DT-心肌黄酶的细胞质，可最大限度地减少半醌的形成和伴随的 O2 消耗。还提供了与其他醌相关的数据。 DT-心肌黄酶可能作为对抗醌毒性的细胞控制装置。
Rat liver microsomes incubated in the presence of NADPH catalyze the oxidation of menadione (2-methyl-1,4-naphthoquinone) by 2 pathways: NADPH-cytochrome P-450 reductase and DT-diaphorase. The former pathway gives rise to labile semiquinones which are readily autooxidized as revealed by a nonstoichiometric NADPH oxidation and a concomitant O2 consumption. The reduction of menadione catalyzed by DT-diaphorase on the other hand results in a relatively stable hydroquinone accompanied by a stoichiometric oxidation of NADPH and no O2 consumption. The total amount of NADPH oxidized by a given amount of menadione reflects the relative contributions of the 2 pathways which can be demonstrated by the addition of selective inhibitors of the 2 enzymes or by treatment of the rats with phenobarbital or 3-methylcholanthrene which preferentially induces NADPH-cytochrome P-450 reductase and DT-diaphorase, respectively. Addition of cytosol, which contains the bulk of cellular DT-diaphorase, minimizes the formation of semiquinones and the concomitant O2 consumption. Data relating to other quinones are also presented. DT-diaphorase probably serves as a cellular control device against quinone toxicity.