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Alterations in the Regulatory Properties of Hepatic Fatty Acid Oxidation and Carnitine Palmitoyltransferase I Activity after Ethanol Feeding and Withdrawal
Author(s) -
Guzmán Manuel,
Castro José
Publication year - 1990
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1990.tb00506.x
Subject(s) - acetaldehyde , ethanol , carnitine palmitoyltransferase i , chemistry , beta oxidation , medicine , endocrinology , carnitine o palmitoyltransferase , fatty acid , carnitine , biochemistry , alcoholic fatty liver , fatty liver , biology , disease
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.