Frey W A, Vallee B L
Proc Natl Acad Sci U S A. 1980 Feb;77(2):924-7. doi: 10.1073/pnas.77.2.924.
Human liver alcohol dehydrogenase (alcohol: NAD" oxidoreductase, EC 1.1.1.1) catalyzes the oxidation of the 3 beta-OH group of digitoxigenin, digoxigenin, and gitoxigenin to their 3-keto derivatives, which have been characterized by high performance liquid chromatography and mass spectrometry. These studies have identified human liver alcohol dehydrogenase as the unknown NAD(H)-dependent liver enzyme specific for the free hydroxyl group at C3 of the cardiac genins; this hydroxyl is the critical site of the genins' enzymatic oxidation and concomitant pharmacological inactivation in humans. Several kinetic approaches have demonstrated that ethanol and the pharmacologically active components of the digitalis glycosides are oxidized with closely similar kcat/Km values at the same site on human liver alcohol dehydrogenase, for which they compete. Human liver alcohol dehydrogenase thereby becomes an important biochemical link in the metabolism, pharmacology, and toxicology of ethanol and these glycosides, structurally unrelated agents that are both used widely. Both the competition of ethanol with these cardiac sterols and the narrow margin of safety in the therapeutic use of digitalis derivatives would seem to place at increased risk those individuals who receive digitalis and simultaneously consume large amounts of ethanol or whose alcohol dehydrogenase function is impaired.
人肝脏乙醇脱氢酶（乙醇：NAD⁺氧化还原酶，EC 1.1.1.1）催化洋地黄毒苷元、地高辛苷元和吉他洛苷元的3β-羟基氧化为它们的3-酮衍生物，这些衍生物已通过高效液相色谱和质谱进行了表征。这些研究已确定人肝脏乙醇脱氢酶是一种未知的依赖NAD(H)的肝脏酶，对强心苷元C3位的游离羟基具有特异性；该羟基是强心苷元在人体内酶促氧化及伴随的药理失活的关键位点。几种动力学方法已证明，乙醇和洋地黄糖苷的药理活性成分在人肝脏乙醇脱氢酶的同一位点上以非常相似的kcat/Km值被氧化，它们在该位点存在竞争。因此，人肝脏乙醇脱氢酶成为乙醇与这些糖苷代谢、药理及毒理学方面的重要生化联系，这两种结构不相关的药物都被广泛使用。乙醇与这些强心甾醇的竞争以及洋地黄衍生物治疗应用中狭窄的安全范围，似乎会使那些接受洋地黄治疗且同时大量饮用乙醇或其乙醇脱氢酶功能受损的个体面临更高风险。
