Lieber C S
Alcohol Research and Treatment Center, Bronx VA Medical Center, New York 10468.
Alcohol Alcohol. 1990;25(2-3):157-76. doi: 10.1093/oxfordjournals.alcalc.a044990.
Ethanol has been shown to have a multitude of acute and chronic interactions with xenobiotic agents, many of which can now be explained on the basis of the existence of a newly recognized microsomal ethanol oxidizing system (MEOS) involving a specific cytochrome P-450 (P450IIE1). Although such a system was proposed already two decades ago, its role was viewed with skepticism: until recently, it was commonly believed that the primary pathway for hepatic ethanol metabolism is due almost exclusively to the activity of cytosolic alcohol dehydrogenase, with a minor contribution from peroxisomal catalase. It is now recognized, however, that liver microsomes (through MEOS) participate in ethanol metabolism. The existence of this system and its inducibility contribute to the metabolic tolerance to ethanol in the alcoholic. Cross induction of other microsomal enzymes also explains the tolerance to many commonly used drugs. Most importantly, the alcohol-inducible form (P450IIE1) has a unique capacity to activate xenobiotic agents to toxic metabolites, thereby explaining the unusual susceptibility of the alcoholic to the adverse effects of other drugs, hepatotoxic agents, carcinogens and even vitamins.
乙醇已被证明与外源性物质存在多种急性和慢性相互作用，现在其中许多相互作用可以基于一种新发现的微粒体乙醇氧化系统（MEOS）的存在来解释，该系统涉及一种特定的细胞色素P - 450（P450IIE1）。尽管这样的系统在二十年前就已被提出，但其作用受到怀疑：直到最近，人们普遍认为肝脏乙醇代谢的主要途径几乎完全归因于胞质醇脱氢酶的活性，过氧化物酶体过氧化氢酶的贡献较小。然而现在人们认识到，肝脏微粒体（通过MEOS）参与乙醇代谢。这个系统的存在及其可诱导性导致了酗酒者对乙醇的代谢耐受性。其他微粒体酶的交叉诱导也解释了对许多常用药物的耐受性。最重要的是，酒精诱导型（P450IIE1）具有将外源性物质激活为有毒代谢物的独特能力，从而解释了酗酒者对其他药物、肝毒性物质、致癌物甚至维生素的不良反应具有异常易感性。
