carbohydrate moieties of lysosomal enzymes as ...

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acetylglucosaminyl phosphate transferase and have demonstrated this activity in ... in a diester linkage between C-1 of N-acetylglucosamine and C-6 o f ...



Mon-S3-3 STEPS IN THE FORMATION OF ASPARAGINE-LINKED CARBOHYDRATE MOIETIES - Stuart Kornfeld, Ira Tabas, Ajit Varki, and Marc Reitman. Washington University School of Medicine, St. Louis, Missouri, U.S.A. Glycosylation of asparagine residues is initiated by the transfer of a large oligosaccharide (GlcgMangGlcNAc2) from a lipid donor to the nascent polypeptide. This oligosaccharide is then processed giving rise to several different end products. In all instances processing is initiated by the removal of the three glucose residues by two distinct glucosidases. High mannose-type oligosaccharides result when no further processing occurs. Complex-type oligosaccharides are formed when processing continues with the removal of 6 of the 9 mannose residues and the addition of outer GlcNAc, Gal and sialic acid residues. The high mannose units of acid hydrolases undergo a specific phosphorylation reaction which generates the recognition marker for the targeting of these enzymes to lysosomes. The initial reaction involves the transfer of N-acetylglucosamine l-phosphate from IIDP-GlcNAc to the 6 hydroxyl of particular mannose residues of the oligosaccharide. The N-acetylglucosamine is removed by a specific a-Nacetylglucosaminyl phosphodiesterase to unmask the targeting function of the underlying phosphomannosyl residue. We have developed an assay for the Nacetylglucosaminyl phosphate transferase and have demonstrated this activity in a number of different tissues. Fibroblasts from six patients with mucolipidoses I1 4 111, conditions characterized by the failure to phosphorylate and target acid hydrolases to lysosomes, have decreased or absent levels o f this enzyme activity. (

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