Glucosamine Itself Mediates Reversible Inhibition of Protein Glycosylation

Abstract

The metabolism of glucosamine in chick embryo fibroblasts was studied at different concentrations of the amino sugar added to the culture medium. In glucose-containing medium the well-known metabolites, UDP-N-acetylglucosamine, N-acetylglucosamine 6-phosphate and N-acetylglucosamine, are detectable after inhibition of glycosylation resulting from glucosamine treatment. Especially when the cells were infected with influenza virus, high intracellular concentrations of non-metabolized glucosamine are demonstrable in addition. Removal of the inhibitor from the medium results in release of the block of influenza virus glycoprotein glycosylation within 10 min. The onset of glycosylation is paralleled by a rapid reduction of intracellular levels of glucosamine without significant changes in the concentrations of its metabolites. Furthermore, concentrations of GDP-mannose, UDP-glucose, and UDP-galactose remain constant for at least 30 min after reversal of the block. It is concluded that glucosamine as such exerts its effects on glycosylation, rather than one of its metabolites being responsible for this effect.