Glycoproteins: their structure, biosynthesis and possible clinical implications

Glycoproteins carrying asparagine-linked N-glycosyl oligosaccharides have many diverse biological functions. The role of the carbohydrate in these functions is often obscure. However, there is evidence that carbohydrate is involved in stabilization of glycoproteins during passage from the rough endoplasmic reticulum to the cell surface, and in recognition phenomena such as receptor-mediated endocytosis, routing of lysosomal hydrolases to the lysosomes, and the spread of cancer cells to secondary sites. The cell surface carbohydrate of some transformed cell lines tends to be more highly branched than that of the non-transformed controls. The control of branching during synthesis of N-glycosyl oligosaccharides resides in the N-acetylglucosaminyltransferases (GlcNAc-transferases) which initiate these branches. There must be at least seven such GlcNAc-transferases to account for the diversity of structures that have been observed. Our laboratory has developed assays for four of these enzymes. Substrate specificity studies on these enzymes have shed light on some of the control mechanisms involved in the synthesis of highly branched structures. Alterations in these control mechanisms may be important in the pathogenesis of cancer and other disease.