Handbook of Glycosyltransferases and Related Genes pp 1659-1665 | Cite as
Map 1: Biosynthetic Pathways of N-Glycans
N-glycan precursors in mammals are synthesized as lipid-linked oligosaccharides (LLO) on the rough endoplasmic reticulum (ER) in the cells as shown in Fig. 147.1. The structure of glycan moiety of these precursors is written as (Glc)3(Man)9(GlcNAc)2. This oligosaccharide is linked by a pyrophosphoryl residue to dolichol moiety, a long-chain (75–105 carbon atoms) polyisoprenoid lipid that acts as a carrier for the oligosaccharide. The dolichol pyrophosphoryl oligosaccharide is synthesized in the ER, in which N-acetylglucosamine, mannose, and glucose residues are added one at a time to dolichol phosphate. The monosaccharide donors include UDP-GlcNAc and GDP-Man for the first seven linkage reactions that occur on the cytosolic side of the ER membrane. In the first two steps, GlcNAc residues are added to the Dol-P by GlcNAc-1-phosphotransferase and then by a GlcNAc-transferase. Next, five mannose residues are added using GDP-Man. After the completion of (Man)5(GlcNAc)2-PP-Dol, the chain flips across the membrane bilayer to become oriented in the lumen of the ER. Sequentially four mannose and three glucose residues are added using Dol-P-Man and Dol-P-Glc. After that, the oligosaccharide is transferred en bloc by an ER enzyme, oligosaccharyltransferase, from the dolichol carrier to an asparagine residue on the nascent polypeptide. The asparagine residue must be in the tripeptide recognition sequence Asn-X-Ser/Thr, where X is any amino acid except proline. In some rare cases, Asn-X-Cys is also utilized for N-glycosylation.