Guzmán M, Castro J
Department of Biochemistry and Molecular Biology I, Faculty of Chemistry, Complutense University, Madrid, Spain.
Alcohol Clin Exp Res. 1990 Jun;14(3):472-7. doi: 10.1111/j.1530-0277.1990.tb00506.x.
The effects of prolonged ethanol feeding on the regulatory properties of both hepatic fatty acid oxidation and carnitine palmitoyltransferase I activity (CPT-I) were studied in rats fed a high-fat diet containing 36% of total calories as ethanol (ethanol group) or an isocaloric amount of carbohydrate (control group). Prolonged ethanol feeding progressively decreased CPT-I activity and increased enzyme sensitivity and sensitization to inhibition by malonyl-CoA in liver mitochondria. Similarly, long-term ethanol feeding progressively increased the sensitivity of CPT-I, as well as that of fatty acid oxidation, to inhibition by 4-hydroxyphenylglyoxylate. Short-term addition of ethanol or acetaldehyde to the incubations markedly increased the sensitivity of CPT-I to inhibition by malonyl-CoA in a subsequent assay in hepatocytes isolated from ethanol-treated rats, but not in cells from control animals. This effect may be mediated by the ethanol- or acetaldehyde-induced increase of intracellular malonyl-CoA levels. The present results show that ethanol feeding to rats leads to profound alterations in the regulatory properties of hepatic CPT-I, which seem to be determinant for the decreased capacity of fatty acid oxidation by the liver in this state. Nevertheless, all the above-mentioned alterations of the fatty acid oxidative system were reversible, disappearing after 2 to 4 days of ethanol withdrawal.
在喂食含36%总热量乙醇的高脂饮食大鼠（乙醇组）或等量热量碳水化合物的大鼠（对照组）中，研究了长期喂食乙醇对肝脏脂肪酸氧化调节特性和肉碱棕榈酰转移酶I活性（CPT-I）的影响。长期喂食乙醇会使肝脏线粒体中CPT-I活性逐渐降低，并增加该酶对丙二酰辅酶A抑制作用的敏感性和致敏性。同样，长期喂食乙醇会使CPT-I以及脂肪酸氧化对4-羟基苯乙酮酸抑制作用的敏感性逐渐增加。在从乙醇处理大鼠分离的肝细胞后续检测中，短期在孵育液中添加乙醇或乙醛会显著增加CPT-I对丙二酰辅酶A抑制作用的敏感性，但在对照动物细胞中则不会。这种效应可能由乙醇或乙醛诱导的细胞内丙二酰辅酶A水平升高介导。目前的结果表明，给大鼠喂食乙醇会导致肝脏CPT-I调节特性发生深刻改变，这似乎是该状态下肝脏脂肪酸氧化能力降低的决定因素。然而，脂肪酸氧化系统的所有上述改变都是可逆的，在停止喂食乙醇2至4天后消失。
