Lieber C S, DeCarli L M, Feinman L, Hasumura Y, Korsten M, Matsuzaki S, Teschke R
Adv Exp Med Biol. 1975;59:185-227. doi: 10.1007/978-1-4757-0632-1_14.
Hepatic metabolism of ethanol to acetaldehyde by the alcohol dehydrogenase (ADH) pathway is associated with the generation of reducing equivalents as NADH. Conversely, reducing equivalents are consumed when ethanol oxidation is catalyzed by the NADPH dependent microsomal ethanol oxidizing system (MEOS). Since the major fraction of ethanol metabolism proceeds via ADH and since the oxidation of acetaldehyde also generates NADH, an excess of reducing equivalents is produced. This explains a variety of effects following acute ethanol administration, including hyperlactacidemia, hyperuricemia, enhanced lipogenesis and depressed lipid oxidation. To the extent that ethanol is oxidized by the alternate MEOS pathway, it slows the metabolism of other microsomal substrates. Following chronic ethanol consumption, adaptive microsomal changes prevail, which include enhanced ethanol and drug metabolism, and increased lipoprotein production. Eventually, injury develops with alterations of the rough endoplasmic reticulum and structural and functional abnormalities of the mitochondria.
乙醇通过乙醇脱氢酶（ADH）途径在肝脏中代谢为乙醛，这与作为还原当量的NADH的生成有关。相反，当乙醇氧化由依赖NADPH的微粒体乙醇氧化系统（MEOS）催化时，还原当量会被消耗。由于大部分乙醇代谢通过ADH进行，并且由于乙醛的氧化也会生成NADH，因此会产生过量的还原当量。这解释了急性乙醇给药后的多种效应，包括高乳酸血症、高尿酸血症、脂肪生成增强和脂质氧化受抑制。就乙醇通过替代的MEOS途径被氧化而言，它会减缓其他微粒体底物的代谢。长期摄入乙醇后，适应性微粒体变化占主导，包括乙醇和药物代谢增强以及脂蛋白生成增加。最终，会出现损伤，伴有粗面内质网的改变以及线粒体的结构和功能异常。
