Metabolic alterations produced in the liver by chronic ethanol administration. Increased oxidative capacity.
Metabolic alterations produced in the liver by chronic ethanol administration. Increased oxidative capacity.
复制标题
长期服用乙醇会导致肝脏代谢改变。
作者：
L. Videla;J. Bernstein;Y. Israel
1. 大鼠连续21-26天给予乙醇（14g/天/ kg）可提高动物代谢乙醇的能力，而肝脏酒精脱氢酶或过氧化氢酶的活性未发生变化。2. 长期用乙醇处理的大鼠肝脏切片与对照动物的肝脏切片相比，O(2)消耗率显著增加（40-60%）。二硝基酚和砷酸盐等解偶联剂经乙醇长期处理后，其作用完全丧失。3. 用琥珀酸盐作为底物时，长期用乙醇处理的动物分离线粒体的状态3或状态4呼吸、ADP/O比、呼吸控制率和二硝基苯酚效应均无变化。以-羟基丁酸盐为底物时，ADP/O比的下降幅度不大，但有统计学意义，而其他参数和二硝基苯酚效应的下降幅度不大。此外，慢性乙醇处理未发现线粒体Mg（2+）活化的腺苷三磷酸酶、二硝基苯酚活化的腺苷三磷酸酶或二硝基苯酚活化的腺苷三磷酸酶/Mg（2+）活化的腺苷三磷酸酶比值的变化。4. 肝微粒体NADPH氧化酶是一种产生H(2)O(2)的系统，经慢性乙醇处理后，其活性提高了80-100%。在这些动物体内甲酸氧化为CO(2)也增加了。理论上，甲酸代谢的增加可以由NADPH氧化酶系统产生的H(2)O(2)的增加加上过氧化氢酶对甲酸盐的过氧化作用来解释。然而，过氧化氢酶系统增加的H(2)O(2)的产量和乙醇的氧化不能占长期乙醇处理动物乙醇代谢增加的10-20%以上。5. 结果表明，慢性乙醇摄入导致线粒体O(2)原位消耗更快，这表明NADH再氧化更快。虽然在分离的线粒体中只观察到线粒体偶联的微小变化，但不能完全排除完整细胞中偶联解耦的可能性。无论机制如何，这些变化都可能导致乙醇和其他内源性底物的代谢增加。
1. Administration of ethanol (14g/day per kg) for 21-26 days to rats increases the ability of the animals to metabolize ethanol, without concomitant changes in the activities of liver alcohol dehydrogenase or catalase. 2. Liver slices from rats chronically treated with ethanol showed a significant increase (40-60%) in the rate of O(2) consumption over that of slices from control animals. The effect of uncoupling agents such as dinitrophenol and arsenate was completely lost after chronic treatment with ethanol. 3. Isolated mitochondria prepared from animals chronically treated with ethanol showed no changes in state 3 or state 4 respiration, ADP/O ratio, respiratory control ratio or in the dinitrophenol effect when succinate was used as substrate. With beta-hydroxybutyrate as substrate a small but statistically significant decrease was found in the ADP/O ratio but not in the other parameters or in the dinitrophenol effect. Further, no changes in mitochondrial Mg(2+)-activated adenosine triphosphatase, dinitrophenol-activated adenosine triphosphatase or in the dinitrophenol-activated adenosine triphosphatase/Mg(2+)-activated adenosine triphosphatase ratio were found as a result of the chronic ethanol treatment. 4. Liver microsomal NADPH oxidase activity, a H(2)O(2)-producing system, was increased by 80-100% by chronic ethanol treatment. Oxidation of formate to CO(2)in vivo was also increased in these animals. The increase in formate metabolism could theoretically be accounted for by an increased production of H(2)O(2) by the NADPH oxidase system plus formate peroxidation by catalase. However, an increased production of H(2)O(2) and oxidation of ethanol by the catalase system could not account for more than 10-20% of the increased ethanol metabolism in the animals chronically treated with ethanol. 5. Results presented indicate that chronic ethanol ingestion results in a faster mitochondrial O(2) consumption in situ suggesting a faster NADH reoxidation. Although only a minor change in mitochondrial coupling was observed with isolated mitochondria, the possibility of an uncoupling in the intact cell cannot be completely discarded. Regardless of the mechanism, these changes could lead to an increased metabolism of ethanol and of other endogenous substrates.