Figure 2

Molecular details of glycan biosynthesis. (a) The glycosylation process can be divided into early (1) and late (2) stages. First, nucleotide-sugar donors are enzymatically prepared from monosaccharides, as illustrated by the conversion of ManNAc into CMP-Sia (1). Nucleotide-sugar donors are assembled by glycosyltransferases into the oligosaccharides that decorate glycoproteins (shown, 2) or glycolipids (not shown). (b) Specific steps in the conversion of dietary sugars (indicated with yellow shading) to nucleotide-sugar donors (pink shading). Arrows represent known enzymatic activities drawn in the direction of the synthesis of nucleotide-sugar donors. It should be noted that the reverse reactions are typically also possible, catalyzed either by the same or other enzymes (adapted from [19]). (c) Nucleotide-sugar donors enter the endoplasmic reticulum (ER) or Golgi lumen through the action of specific antiport transporters. Oligosaccharides are synthesized by sequential action of the appropriate glycosyltransferases as they traverse the secretory apparatus. The process shown is typical of O-linked (serine- or threonine-attached) glycoprotein biosynthesis. For N-linked glycoproteins (not shown), a core oligosaccharide is assembled in the cytosol, then transported into the ER where it is processed by glycosidases, and then further elaborated by glycosyltransferases; details of this complex process are described elsewhere [10].