The catabolism of mammalian glycoproteins. Comparison of the storage products in bovine, feline and human mannosidosis

Abstract

Analysis of the neutral urinary oligosaccharides in bovine, feline and human mannosidosis by thin-layer and gel-permeation chromatography showed that the patterns of stored oligosaccharides in the 3 species are different. In bovine and feline mannosidosis the most abundant urinary oligosaccharide is also the most abundant in the tissues of each species. The predominant oligosaccharides were purified by a combination of gel-filtration, ion-exchange and thin-layer chromatography and shown to contain only mannose and N-acetylglucosamine by GLC and GLC-mass spectrometry. The probable composition and size of each oligosaccharide were predicted from its chromatographic properties, sugar composition and the known structure of asparagine-linked oligosaccharides. The bovine and feline oligosaccharides belonged to a homologous series of general composition Mann(GlcNAc)2, whereas the human oligosaccharides belong to a different series, ManlnGlcNAc suggesting that lysosomal endohexosaminidase is not present in bovine and feline tissues. The predominant feline storage product, Man3(GlcNAC)2, was the expected storage product from the catabolism of complex asparagine-linked glycans. In contrast, the predominant bovine oligosaccharide, Man2(GlcNAc)2, probably lacks one of the .alpha.-linked mannose residues in the core region. A similar situation occurs in human mannosidosis. It is predicted that in these species either the residual mutant .alpha.-D-mannosidase [EC 3.2.1.24] retains activity towards one of the core .alpha.-linked mannose residues or another form of lysosomal .alpha.-D-mannosidase that is unaffected in these disorders occurs. The differences in storage products are due to differences in the catabolic pathways of glycoproteins among the species.