Hasumura Y, Teschke R, Lieber C S
J Pharmacol Exp Ther. 1975 Aug;194(2):469-74.
The activity of the hepatic microsomal ethanol-oxidizing system (MEOS) was compared with the content of three forms of cytochrome P-450. Measurements were also made of the activity of microsomal reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, the enzyme which generates H2O2 in microsomes and which has been considered by some to be the rate-limiting step of MEOS activity. Ethanol feeding to rats for 4 to 5 weeks significantly enhanced the activities of MEOS and NADPH oxidase by 102 and 62%, respectively. Concomitantly, form I of cytochrome P-450 was increased by 88% (P less than .001). Acute administration of a large dose of ethanol to animals pretreated chronically with ethanol enhanced MEOS activity by 21% (P less than .05), whereas NADPH oxidase activity remained unchanged. In addition, an acute dose of ethanol enhanced form I of cytochrome P-450 by 20% (P less than .05); thus its increase was comparable to that of MEOS activity. Pretreatment of rats with phenobarbital increased the specific activity of microsomal NADPH oxidase by 40% (P less than .05) but not that of MEOS. By contrast, CCl4 administration to rats diminished MEOS activity by 33% (P less than .01), whereas NADPH oxidase activity remained unchanged. The CCl4 treatment was found to decrease significantly all three forms of cytochrome P-450: form I by 45%, form II by 56% and form III by 24%. These results suggest that in the presence of NADPH microsomes oxidize ethanol to acetaldehyde by a process which involves, at least in part, the form I of cytochrome P-450 and in which H2O2 generation by NADPH oxidase is not the rate-limiting step.
将肝脏微粒体乙醇氧化系统（MEOS）的活性与三种细胞色素P - 450的含量进行了比较。还测定了微粒体还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶的活性，该酶在微粒体中产生过氧化氢，并且一些人认为它是MEOS活性的限速步骤。给大鼠喂食乙醇4至5周分别使MEOS和NADPH氧化酶的活性显著提高了102%和62%。同时，细胞色素P - 450的I型增加了88%（P小于0.001）。对长期用乙醇预处理的动物急性给予大剂量乙醇使MEOS活性提高了21%（P小于0.05），而NADPH氧化酶活性保持不变。此外，急性剂量的乙醇使细胞色素P - 450的I型增加了20%（P小于0.05）；因此其增加与MEOS活性的增加相当。用苯巴比妥预处理大鼠使微粒体NADPH氧化酶的比活性提高了40%（P小于0.05），但MEOS的比活性未提高。相比之下，给大鼠注射四氯化碳使MEOS活性降低了33%（P小于0.01），而NADPH氧化酶活性保持不变。发现四氯化碳处理使所有三种细胞色素P - 450均显著降低：I型降低45%，II型降低56%，III型降低24%。这些结果表明，在存在NADPH的情况下，微粒体通过一个至少部分涉及细胞色素P - 450的I型的过程将乙醇氧化为乙醛，并且在该过程中NADPH氧化酶产生过氧化氢不是限速步骤。
