Lysosomal degradation of Asn-linked glycoproteins.
Catabolism of Asn-linked glycoproteins to monosaccharides and amino acids occurs in lysosomes. Break-down must be complete to avoid lysosomal storage diseases that occur when fragments as small as dimers are left undigested. Recent results have clarified several aspects of Asn-linked glycoprotein catabolism in mammals. First, degradation of the oligosaccharide portion is accomplished by exo-glycosidases, which act only from the nonreducing end of chains to release sugar monomers as products. In contrast, proteolysis can proceed from both end and internal points along the polypeptide to eventually yield free amino acids. A second important feature of the glycoprotein disassembly pathway is that the hydrolytic steps can be grouped into two sets of ordered reactions: I) stepwise hydrolysis of the major portion of the oligosaccharide chains by a set of exoglycosidases, and II) ordered disassembly of the protein and the oligosaccharide-to-protein linkage region. Process II can vary at a single reaction step depending on the species in which degradation takes place. Thus, the last step of reaction sequence II can be either: 1) hydrolysis of the actual peptide-to-carbohydrate linkage, or 2) removal of the reducing-end GlcNAc from a previously freed oligosaccharide. The latter cleavage is catalyzed by the lysosomal glycosidase chitobiase. Chitobiase has been found only in humans and rats and not in other mammals (dogs, cats, goats, sheep, cats, or cattle). The hydrolytic mechanism of this enzyme is unique as it appears to be a reducing-end glycosidase and can be viewed as an accessory step in the human and rat digestive pathways. The species that lack this enzyme likely rely on exo-beta-D-glucosaminidase to cleave GlcNAc from both outer chain residues and the chitobiose moiety at the protein-to-carbohydrate linkage.
Aronson
N N
NN
Department of Molecular and Cell Biology, Pennsylvania State University, University Park 16802.
Kuranda
M J
MJ
D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D001216:Asparagine / Q000378:metabolism*; D002240:Carbohydrate Sequence; D006023:Glycoproteins / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008247:Lysosomes / Q000201:enzymology*; D008969:Molecular Sequence Data; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D006023:Glycoproteins; D001216:Asparagine; D006026:Glycoside Hydrolases; D000118:Acetylglucosaminidase; D001619:beta-N-Acetylhexosaminidases