Glycosylation and Disease
Published Online: 15 SEP 2010
Copyright © 2001 John Wiley & Sons, Ltd. All rights reserved.
How to Cite
Rhodes, J., Campbell, B. J. and Yu, L.-G. 2010. Glycosylation and Disease. eLS. .
- Published Online: 15 SEP 2010
Glycosylation is the process of attachment of sugar molecules, usually in chains (oligosaccharides), to proteins and lipids to form the glycoproteins and glycolipids found in eukaryotic and some prokaryotic organisms. The presence of oligosaccharides on a protein can have substantial effects on its size, stability, charge and antigenicity. The varying structure, branching and substitution of the carbohydrates in an oligosaccharide results in much greater diversity than would be achieved for a peptide with an equivalent number of residues. Acquired alterations in glycosylation occur in cancer and inflammation and may have particularly important functional consequences when they affect mucosae. They also have the potential to affect pathogen–host and other cell–cell interactions. Congenital glycosylation disorders most commonly affect N-glycosylation and affect development in diverse ways. There is increasing evidence of the importance of interactions between carbohydrate structures and carbohydrate-binding proteins (lectins) which may be extrinsic (dietary or microbial) or intrinsic (mammalian galectins or siglecs).
Glycosylation occurs as N- and O-linked (mucin type) oligosaccharides (glycans) on glycoproteins and as glycolipids.
Variation in sequence, linkage and substitution of carbohdrates in a glycan means that a relatively short glycan can have many more variations (glycoforms) than a peptide with an equivalent number of amino acids.
Variations in glycan structure can result from a range of different mechanisms that include altered glycosyltransferase and glycosidase activity, Golgi acidification and structure, donor and acceptor availability.
Cell–cell and cell–microbe interactions are often driven by interactions between lectins on one cell and the relevant carbohydrate (glycan) receptor on the other cell.
Mucins are heavily glycosylated, particularly with O-linked glycans and this gives them their protective properties.
Mammalian lectins include a family of galactose-binding lectins called galectins that interact with some of the glycans that show increased expression in epithelial cancers with increased cancer cell to endothelial adherence and increased metastasis as a consequence.
Foodstuffs, particularly legumes, contain lectins some of which resist digestion and may have biologically significant interactions with the intestinal epithelium.
A wide range of rare congenital dosorders of glycosylation have been recognised – these have many and varied developmental consequences.
Some of the developmental glycosylation disorders can be screened for by isoelectric focusing of serum glycoproteins.
- blood groups;
- cell–cell interaction;
- epithelial–microbe interaction