Alterations in the regulatory properties of hepatic fatty acid oxidation and carnitine palmitoyltransferase I activity after ethanol feeding and withdrawal.
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.
Guzmán
M
M
Department of Biochemistry and Molecular Biology I, Faculty of Chemistry, Complutense University, Madrid, Spain.
Castro
J
J
D000079:Acetaldehyde / Q000378:metabolism; D000217:Acyltransferases / Q000378:metabolism*; D000437:Alcoholism / Q000201:enzymology*; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000431:Ethanol / Q000009:adverse effects*; D005227:Fatty Acids / Q000378:metabolism*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism; D008930:Mitochondria, Liver / Q000201:enzymology*; D010084:Oxidation-Reduction; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000201:enzymology*
D005227:Fatty Acids; D007527:Isoenzymes; D000431:Ethanol; D008316:Malonyl Coenzyme A; D000217:Acyltransferases; D002334:Carnitine O-Palmitoyltransferase; D000079:Acetaldehyde