Effects of ethanol on free coenzyme A, free carnitine and their fatty acid esters in rat liver

Abstract

1. 1. Ethanol increases liver triglycerides. In order to elucidate the mechanism of this fat deposit, the effect of ethanol on CoA, carnitine and their fatty acid esters in the liver was investigated. 2. 2. A single dose of ethanol (5 g/kg) increases CoA concentration in the liver of rats kept on a standard diet. 2 h following the administration of ethanol, the ratio long-chain acyl-CoA/free CoA remains nearly unchanged as compared to control animals. After 12 h, when liver triglycerides are markedly elevated, this ratio shifts distinctly in favor of the long-chain acyl-CoA. 3. 3. In protein-deficient rats, the long-chain acyl-CoA content in the liver increases markedly as compared to controls given a standard diet, while the level of free CoA drops. Under these conditions, acute ethanol application results in extremely high long-chain acyl-CoA levels. 4. 4. After ethanol administration, carnitine concentration alters in a similar way to CoA concentration. However, after ethanol administration, the increase of longchain acyl-carnitine is much less pronounced than the increase of acyl-CoA. Thus, the ratio long-chain acyl-carnitine/free carnitine shows minor alterations during ethanol oxidation. 5. 5. From these results, it is suggested that under conditions in which ethanolinduced lipid accumulation in the liver is observed, fatty acid synthesis is reduced by a negative feedback inhibition of the acetyl-CoA carboxylase reaction by high levels of long-chain acyl-CoA. These findings support the assumption that fat infiltration in the liver after acute ethanol administration is mainly caused by enhanced mobilization of free fatty acids from adipose tissue and not by stimulation of fatty acid synthesis in the liver.