Role of acetaldehyde in the ethanol-induced impairment of glycoprotein metabolism in rat liver slices.
The mechanism responsible for ethanol-induced changes in the glycosylation of proteins was investigated in rat liver slices. Ethanol (5 to 50 mM) decreased [1-14C]glucosamine and [14C]leucine incorporation into total liver and microsomal proteins and greatly inhibited incorporation into medium (secretory) proteins. Pyrazole prevented the inhibition of glycoprotein synthesis by ethanol. Additions of methylene blue or pyruvate, which corrected the disordered redox state caused by ethanol oxidation, did not reverse the inhibitory effects of ethanol on glycosylation. Sorbitol, which mimics ethanol in generating reducing equivalents in the hepatocyte, also inhibited glycosylation; however, fructose, the immediate oxidation product of sorbitol, similarly inhibited glycoprotein synthesis without altering the redox state. When low levels of acetaldehyde (0.12 to 0.70 mM) were maintained in the medium by means of infusion, a significant inhibition of glycoprotein synthesis was observed. Acetate did not impair glycosylation. These data suggest that the ethanol-induced impairment of glycoprotein synthesis and secretion is a consequence of ethanol metabolism and further suggest that this inhibition is attributable to acetaldehyde formation rather than to the altered redox state resulting from ethanol oxidation.
D000079:Acetaldehyde / Q000494:pharmacology; D000085:Acetates / Q000494:pharmacology; D000818:Animals; D003864:Depression, Chemical; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D005632:Fructose / Q000494:pharmacology; D005944:Glucosamine / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D066298:In Vitro Techniques; D007930:Leucine / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008751:Methylene Blue / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D013012:Sorbitol / Q000494:pharmacology
D000085:Acetates; D006023:Glycoproteins; D011720:Pyrazoles; D005632:Fructose; D000431:Ethanol; D013012:Sorbitol; D007930:Leucine; D000079:Acetaldehyde; D005944:Glucosamine; D008751:Methylene Blue