Coordination between enzyme specificity and intracellular compartmentation in the control of protein-bound oligosaccharide biosynthesis.

This laboratory has developed schemes for the control of biosynthesis of N- and O-glycosyl oligosaccharides based on studies in cell-free systems of glycosyl-transferase substrate specificities. These schemes are based on assumptions that may not be universally correct. For example, we have ignored the possible compartmentation of reactions in different cells or in different organelles within a cell. Recent evidence has indicated that the Golgi apparatus has at least three functionally distinct regions (cis, medial and trans). The addition of galactosyl and sialyl residues to the antennae of complex and hybrid N-glycans probably occurs entirely within the trans-cisternae while the N-acetylglucosaminyl-transferases which initiate these antennae appear to be located in a denser region of the Golgi (cis and/or medial cisternae). We have constructed a modified scheme for the biosynthesis of the antennae of N-glycans. This scheme combines our substrate specificity data (H. Schachter, S. Narasimhan, P. Gleeson and G. Vella, 1983, Can. J. Biochem. Cell Biol., 61, 1049-1066) with compartmentation data. It provides a basis for understanding the control of glycoprotein synthesis in normal tissues and in certain lectin-resistant mutant cell lines.