Selective impairment of glycoprotein metabolism by ethanol and acetaldehyde in rat liver slices

Michael F. Sorrell, Dean J. Tuma

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

The mechanism responsible for the ethanol-induced alterations in glycoprotein metabolism was investigated. Inhibitors of peptide synthesis were utilized in a liver slice system to equalize the pool of protein acceptors available for glycosylation in the control, ethanol- and acetaldehyde-treated slices. The presence of puromycin or cycloheximide in the medium almost completely inhibited the incorporation of [14C]leucine into liver and medium proteins and reduced [14C]glucosamine incorporation into these fractions by 50%. Ethanol (10 mm) alone decreased the glycosylation of hepatocellular proteins and greatly inhibited the output of secretory glycoproteins. When puromycin (or cycloheximide) and ethanol were both present, a further marked decrease in the specific activity of secretory glycoproteins was observed when compared to the slices containing puromycin alone; however, the specific activity of liver glycoproteins was increased. When low concentrations of acetaldehyde, similar to levels generated during in vivo ethanol oxidation, were maintained in the medium by infusion, an identical inhibition of [14C]glucosamine incorporation into medium proteins was observed both in the presence and absence of inhibitors of protein synthesis. The effects of ethanol on hepatic macromolecular secretion independent of its effect on synthesis were determined by prelabeling proteins in a liver slice system with either [14C]leucine or [14C]glucosamine. Both ethanol and acetaldehyde impaired the secretion of these prelabeled proteins into the medium. These results demonstrate that ethanol or its metabolite, acetaldehyde, alter glycoprotein metabolism independent of its effect on general protein synthesis, and suggest that impaired secretion of glycoproteins may be the major manifestation of this altered metabolism.

Original languageEnglish (US)
Pages (from-to)200-205
Number of pages6
JournalGastroenterology
Volume75
Issue number2
DOIs
StatePublished - Aug 1978

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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