Mitochondrial Functions in an Ethanol-induced Fatty Liver

作者：Ellen R. Gordon · 发表于：Journal of Biological Chemistry · 年份：1973 · DOI：10.1016/s0021-9258(19)43224-9 · 被引用次数：117 · 研究领域：Alcohol Consumption and Health Effects、Metabolism and Genetic Disorders、Metabolomics and Mass Spectrometry Studies

Abstract Marked alterations in the functions of hepatic mitochondria have been observed in male Sprague-Dawley rats fed a nutritionally adequate diet having 36% of its caloric content supplied by ethanol. A direct causal relationship exists between changes in mitochondrial function and abnormal accumulation of lipid in the liver. When ethanol forms a significant part of the diet, the reducing equivalents required for the respiratory chain arise mainly from the oxidation of ethanol rather than β oxidation of fatty acids. This simple shift in metabolism appears to be the basis for the biochemical change producing the observed alterations in mitochondrial function. A significant decrease in the translocation of ADP across the mitochondrial membrane was observed which was associated with an increase in the hepatic level of long chain acyl coenzyme A derivatives of fatty acids, which have been shown to impede this metabolic step. This explains the lowering of the respiratory activity and lack of respiratory control which has been observed in the mitochondria isolated from an ethanol-induced fatty liver. This transition from State 3 to 4 in the mitochondria explains the observed decrease in the flux of substrate through the tricarboxylic acid cycle, the shift in the oxidation-reduction state of the mitochondria to a more reduced level, and the decreased synthesis of ATP in the liver of these animals exhibiting a fatty liver.