Possible role of acetyl-CoA in the inhibition of CoA biosynthesis by ethanol in rats.
Ethanol, both administered to rats in vivo and added to cultured hepatocyte incubations, inhibits the conversion of [14C]pantothenate to coenzyme A (CoA). Data suggesting that the inhibition by ethanol involves its oxidation to acetate were obtained with rat hepatocytes maintained in primary culture. Ethanol, acetaldehyde and acetate were approximately equally effective inhibitors of [14C]pantothenate conversion to CoA (46-71%) and had no effect on uptake of [14C]pantothenate by hepatocytes. In the presence of saturating levels of acetate, acetaldehyde had no additional inhibitory effect. Cyanamide and diethyldithiocarbamate decreased the inhibition by acetaldehyde at the same concentration (10 microM), which saturated their ability to inhibit acetaldehyde oxidation. Studies with an isolated pantothenate kinase preparation showed that, of the ethanol metabolites, only acetyl-CoA was an effective inhibitor. Acetate and butyrate, which were both inhibitors of [14C]pantothenate conversion to CoA, increased the acetyl-CoA and decreased the free, unacylated CoA (CoASH) content of the cultured hepatocytes. The data were consistent with a mechanism for the inhibitory effect of ethanol that involves inhibition of pantothenate kinase by acetyl-CoA, but did not exclude a possible role of additional regulatory factors.
D000079:Acetaldehyde / Q000494:pharmacology; D000085:Acetates / Q000494:pharmacology; D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003065:Coenzyme A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D003484:Cyanamide / Q000494:pharmacology; D004050:Ditiocarb / Q000494:pharmacology; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D010205:Pantothenic Acid / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor); D051381:Rats
D000085:Acetates; D010205:Pantothenic Acid; D000431:Ethanol; D003484:Cyanamide; D000105:Acetyl Coenzyme A; D004050:Ditiocarb; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase; D000079:Acetaldehyde; D003065:Coenzyme A