Thurman R G, McKenna W R
Adv Exp Med Biol. 1975;56:57-76. doi: 10.1007/978-1-4684-7529-6_3.
The primary pathway of hepatic ethanol metabolism involves alcohol dehydrogenase. Hydrogen generated from ethanol metabolism enters the mitochondrial space most likely as malate over a substrate shuttle mechanism, and is subsequently oxidized by the mitochondrial respiratory chain. The rate-limiting step in this overall multicompartmental process is the rate of reduced cofactor (NADH) reoxidation by the respiratory chain. Since the electron flux in the respiratory chain is controlled by the ADP supply, alcohol dehydrogenase-dependent ethanol metabolism can be activated by perturbations which circumvent the rate-limiting step, such as artificial electron acceptors, gluconeogenic precursors, and uncoupling agents. Moreover, an ATP utilizing process is responsible for the stimulation of ethanol metabilism observed following chronic pretreatment with ethanol. In perfused rat liver catalase also participates in ethanol metabolism to a lesser extent than alcohol dehydrogenase. Quantitative assessments indicate that the predominant ethanol oxidase at low ethanol concentrations (less than 20 mM) is a alcohol dehydrogenase; however, at higher ethanol concentrations, a significant portion of total ethanol metabolism (up to 50%) is mediated by catalase-hydrogen peroxide complex. This pathway is limited by the rate of generation of hydrogen peroxide in the hepatocyte, and can be stimulated with substrates for intraperoxisomal hydrogen peroxide generation such as glycolate, urate and D-amino acids. Considerable evidence implicates catalase-hydrogen peroxide complex in the mechanism of NADPH-dependent microsomal ethanol oxidation.
肝脏乙醇代谢的主要途径涉及乙醇脱氢酶。乙醇代谢产生的氢最有可能通过底物穿梭机制以苹果酸的形式进入线粒体空间，随后被线粒体呼吸链氧化。在这个多隔室的整体过程中，限速步骤是呼吸链对还原型辅因子（NADH）的再氧化速率。由于呼吸链中的电子通量受ADP供应的控制，依赖乙醇脱氢酶的乙醇代谢可被绕过限速步骤的干扰因素激活，如人工电子受体、糖异生前体和解偶联剂。此外，一个消耗ATP的过程负责在乙醇慢性预处理后观察到的乙醇代谢刺激。在灌注的大鼠肝脏中，过氧化氢酶在乙醇代谢中的参与程度也低于乙醇脱氢酶。定量评估表明，在低乙醇浓度（小于20 mM）时，主要的乙醇氧化酶是乙醇脱氢酶；然而，在较高乙醇浓度下，总乙醇代谢的很大一部分（高达50%）由过氧化氢酶-过氧化氢复合物介导。该途径受肝细胞中过氧化氢生成速率的限制，并且可以用过氧化物酶体内过氧化氢生成的底物如乙醇酸、尿酸和D-氨基酸来刺激。大量证据表明，过氧化氢酶-过氧化氢复合物参与了依赖NADPH的微粒体乙醇氧化机制。
