A PATHOPHYSIOLOGIC ROLE FOR ALCOHOL DEHYDROGENASE: IS RETINOL ITS “NATURAL” SUBSTRATE? *
A PATHOPHYSIOLOGIC ROLE FOR ALCOHOL DEHYDROGENASE: IS RETINOL ITS “NATURAL” SUBSTRATE? *
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乙醇脱氢酶的病理生理作用：视黄醇是其“天然”底物吗？
DOI：
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发表时间：
1976
影响因子：
5.2
通讯作者：
R. H. Steinberg
中科院分区：
文献类型：
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作者：
N. Raskin;K. Sligar;R. H. Steinberg
过量使用乙醇（乙醇）与几个器官的结构和功能的改变有关。酒精性疾病引起了关于酒精的直接毒性作用的相对重要性和通常与慢性酒精中毒有关的营养缺乏的影响的争论。最近的证据表明，肝脏疾病。!心，？和骨髓。3，虽然营养不足加剧和加速，可能是由酒精的细胞毒性作用。酒精的细胞毒性机制尚不确定;其氧化产物乙醛是一种已知的细胞毒素，可能是这些疾病发病机制中的一个重要因素。1. I. L. 1），乙醇氧化的催化剂，也可能涉及。如果确定了这种酶的内源性或"天然"底物，则毒性机制可能是乙醇与其内源性底物之间的竞争性抑制。肝脏A D H具有低底物特异性，其对乙醇的Km相对较高，这一特性支持了A D H的重要作用可能是催化某些尚未鉴定的"天然"底物的氧化的观点。维生素A醇，即视黄醇，是肝脏脱氢酶的底物. ~我们已经验证了视黄醇是体内A D H底物的假设。由于维生素A代谢及其与暗适应过程的关系已经得到了相当好的描述，“眼睛被用作这些研究的模型：
Excessive use of ethyl alcohol (ethanol) is associated with alterations in the structure and function of several organs. The alcoholic disorders have given rise to controversy over the relative importance of a direct toxic action of alcohol and the effects of the nutritional deficiencies that are often associated with chronic alcoholism. Recent evidence suggests that disorders of the liver.! heart,? and bone marrow. 3 although aggravated and accelerated by nutritional inadequacies, are probably caused by cytotoxic actions of alcohol. The mechanism of alcohol's cytotoxicity is uncertain; the product of its oxidation, acetaldehyde, is a known cytotoxin and may be a n important factor in the pathogenesis of these disorders.4.5 Alcohol dehydrogenase (ADH) (a1cohol:NAD' oxidoreductase, E.C. 1 . I . l . l ) , the catalyst of ethanol oxidation, may also be implicated. If the endogenous or "natural" substrate of this enzyme were identified, a mechanism of toxicity may be competitive inhibition between ethanol and its endogenous substrate. Hepatic A D H is of low substrate specificity, and its Km for ethanol is relatively high,h characteristics supportive of the idea that an important role of A D H may be to catalyze the oxidation of.some as yet unidentified "natural" substrate. Vitamin A alcohol, retinol, is a substrate of liver A D H in ~ i r r o . ~ We have tested the hypothesis that retinol is a substrate of A D H in vivo. Because vitamin A metabolism and its relationship to the dark adaptation process has been fairly well delineated," the eye has been used as a model for these studies: