Selection of radioactive precursors for metabolic labelling of mucus glycoproteins

Abstract

From these results, it is clear that certain oligosaccharides are much better substrates than others for each a-mannosidase and that for each substrate, certain mannose residues are preferentially cleaved. Each enzyme degrades the oligosaccharides by ii specific pathway, which is governed by steric accessibility. resulting from the conformation o f the oligosaccharide a s it is hound by the enzyme.T h e substrate specificities for the human, hovine. and feline lysosomal u-mannosidases. together with the absence in animals other than humans and rodents of lysosomal endo-N-acetyl-~-~-glucosaminidase [ 1 I], offer some explanation of the patterns of oligosaccharides accumulated in tissues and excreted in urines of humans and animals with a-mannosidosis [ 1-3. 121. T h e resistance of the core a( 1 -(,)-linkage t o the major human lysosomal u-mannosidase supports the hypothesis that the hydrolysis of this linkage is catalysed by another activity [ 131. Similarly, the facile hydrolysis of the core a( 1 -3)-linkagc by the human enzyme is consistent with the presence o f this linkage in the major urinary oligosaccharide in the absence of the enzyme.T h e well-dcfined specificities for oligosaccharide structures suggest parallels between the catabolic enzymes. and the a-mannosidases involved in the processing of N-linked glycans j 8. 101. This investigationWIS supported h y grant HI>-? I OX7 f r o m the