Horie S
Department of Biochemistry, School of Medicine, Kitasato University, Kanagawa, Japan.
Kitasato Arch Exp Med. 1990 Apr;63(1):11-30.
DT-diaphorase [NAD(P)H dehydrogenase (quinone), EC 1.6.99.2] is a flavoprotein enzyme widely distributed in the cytosolic fractions of various animal tissues. It is also called menadione reductase or NAD(P)H-quinone reductase and catalyzes NAD(P)H-dependent 1-, 2- or 4-electron reduction of certain redox dyes, aromatic nitro compounds, aromatic C-nitroso compounds and probably azo-dyes, as well as menadione (vitamin K3) and other quinones. Dicumarol exerts characteristic inhibition on DT-diaphorase, whereas serum albumin and certain non-ionic detergents exert activation. Excessive concentrations of many of the electron acceptors inhibit the activity of this enzyme. The physiological significance of DT-diaphorase is still obscure because the physiological vitamins (K1 and K2) and coenzyme Q10 are difficult to reduce with this enzyme. Results of recent studies suggest that DT-diaphorase prevents formation of active oxygen species. Activities in liver and other tissues are known to be enhanced by administration of chemicals including certain carcinogens such as 3-methylcholanthrene (3-MC), anti-oxidants such as 3-tert-butyl-4-hydroxyanisole (BHA), and other compounds. Both basal and induced activities vary considerably with tissue, sex, strain and species of animals. The strain variations in activities in rat and mouse liver are known to be inherited, and the trait of hereditary transmission can be adequately explained by postulating two loci of genes or gene clusters regulating the activity. Resistance of animals to various toxic or carcinogenic substances may be promoted by BHA administration and depressed by dicumarol administration. Thus, attention has been focused on the role played by DT-diaphorase in the detoxication of foreign compounds. Knowledge on strain variations in basal and induced activities of tissue DT-diaphorase is of potential value when choosing a rat or mouse strain suitable for studying the toxic effects of drugs, especially drugs expected to be detoxified by reductive metabolism. With future progress in research on DT-diaphorase, this enzyme might be applied to prophylactic and therapeutic medicine.
DT-黄递酶[NAD(P)H脱氢酶(醌)，EC 1.6.99.2]是一种黄素蛋白酶，广泛分布于各种动物组织的胞质部分。它也被称为甲萘醌还原酶或NAD(P)H-醌还原酶，催化某些氧化还原染料、芳香族硝基化合物、芳香族亚硝基化合物以及可能的偶氮染料、甲萘醌(维生素K3)和其他醌类的NAD(P)H依赖性1-、2-或4-电子还原反应。双香豆素对DT-黄递酶有特异性抑制作用，而血清白蛋白和某些非离子去污剂则有激活作用。许多电子受体的过量浓度会抑制该酶的活性。DT-黄递酶的生理意义仍不清楚，因为生理性维生素(K1和K2)和辅酶Q10很难被该酶还原。最近的研究结果表明，DT-黄递酶可防止活性氧的形成。已知通过给予包括某些致癌物如3-甲基胆蒽(3-MC)、抗氧化剂如3-叔丁基-4-羟基茴香醚(BHA)等化学物质以及其他化合物，可增强肝脏和其他组织中的活性。基础活性和诱导活性在不同组织、性别、动物品系和物种之间有很大差异。已知大鼠和小鼠肝脏中活性的品系差异是可遗传的，通过假定两个调节活性的基因位点或基因簇可以充分解释遗传传递的特征。给予BHA可促进动物对各种有毒或致癌物质的抗性，而给予双香豆素则会降低这种抗性。因此，人们将注意力集中在DT-黄递酶在对外源化合物解毒中的作用上。当选择适合研究药物尤其是预期通过还原代谢解毒的药物的毒性作用的大鼠或小鼠品系时，了解组织DT-黄递酶基础活性和诱导活性的品系差异具有潜在价值。随着DT-黄递酶研究的未来进展，这种酶可能会应用于预防医学和治疗医学。
