Talalay P, Benson A M
Adv Enzyme Regul. 1982;20:287-300. doi: 10.1016/0065-2571(82)90021-8.
NAD(P)H:quinone reductase exhibits broad specificity in the reduction of endogenous and exogenous quinones and quinone imines, such as those derived from polycyclic aromatic carcinogens, phenolic steroids, vitamin K, and numerous therapeutic drugs. This enzyme is found in several cell compartments and is widely distributed among tissues. In contrast to several other flavoprotein dehydrogenases, quinone reductase catalyzes obligatorily two electron reductions. Extensive studies by Huggins and by others have shown that the quinone reductase in liver and some other tissues of rats is inducible by various polycyclic hydrocarbons and aromatic amines, as well as by certain azo dyes. Huggins perceived that the relative effectiveness of such compounds in inducing quinone reductase correlated with their abilities to protect against toxicity and carcinogenesis. Certain antioxidants are also known to protect against the tumorigenic and toxic effects of carcinogens. Studies on the mechanisms underlying the protective effects of BHA, BHT, ethoxyquin, and disulfiram have revealed that these compounds alter the activity profiles of several enzymes which metabolize carcinogenic and toxic compounds. We have observed that quinone reductase specific activity is increased markedly in mouse liver and several extrahepatic tissues in response to dietary BHA, ethoxyquin, and disulfiram, whereas BHT has been shown by others to enhance this enzymatic activity in rat liver. These findings confirm and extend the correlation between the ability to elevate quinone reductase activity and to confer protection against carcinogenesis and toxicity. The broad specificity of quinone reductase, its apparent inability to catalyze one electron reductions of quinones, its widespread distribution, and its inducibility by a variety of structurally dissimilar protective compounds, suggest that quinone reductase may play a significant local protective role in various regions of the cell.
NAD(P)H：醌还原酶在还原内源性和外源性醌及醌亚胺时表现出广泛的特异性，这些醌及醌亚胺来源于多环芳烃致癌物、酚类甾体、维生素K以及众多治疗药物。这种酶存在于多个细胞区室中，并且在组织中广泛分布。与其他几种黄素蛋白脱氢酶不同，醌还原酶强制催化双电子还原反应。哈金斯等人的大量研究表明，大鼠肝脏和其他一些组织中的醌还原酶可被各种多环烃、芳香胺以及某些偶氮染料诱导。哈金斯认为，这类化合物诱导醌还原酶的相对效力与其预防毒性和致癌作用的能力相关。某些抗氧化剂也已知可预防致癌物的致瘤和毒性作用。对丁基羟基茴香醚（BHA）、二丁基羟基甲苯（BHT）、乙氧喹和双硫仑保护作用潜在机制的研究表明，这些化合物会改变几种代谢致癌和有毒化合物的酶的活性谱。我们观察到，在小鼠肝脏和一些肝外组织中，膳食中的BHA、乙氧喹和双硫仑会使醌还原酶的比活性显著增加，而其他人已表明BHT可增强大鼠肝脏中的这种酶活性。这些发现证实并扩展了提高醌还原酶活性的能力与预防致癌作用和毒性之间的相关性。醌还原酶的广泛特异性、其显然无法催化醌的单电子还原反应、其广泛分布以及其可被多种结构不同的保护化合物诱导，表明醌还原酶可能在细胞的各个区域发挥重要的局部保护作用。
