Abstract
In eukaryotic cells glycoproteins can have a myriad of mature oligosaccharide structures attached to one to ten specific asparagine residues in a protein. Biosynthesis of these diverse structures begins with common steps involving a polyisoprenol as a carrier lipid. The common biosynthetic steps that occur prior to transfer of an oligosaccharide from the lipid carrier to the nascent protein are the subject of this minireview. Specific enzymatic reactions and the regulation of the reactions involved in the synthesis of the lipid carrier, dolichyl phosphate, and the assembly of Glc3 Man9GlcNAc2-P-P-dolichol are discussed, as are the mechanisms of regulation of the overall glycosylation process itself. Dolichol is a family of isomers consisting of 17-21 isoprenyl groups, with the α isoprenyl group saturated. All cells synthesize dolichol beginning with acetate, sharing the cholesterol biosynthetic pathway through farnesyl pyrophosphate. Beyond this intermediate, cis-polyprenyl transferase, polyprenyl reductase, and a pyrophosphatase combine to synthesize dolichyl phosphate. Dolichyl phosphate is a pivotal intermediate, serving as the substrate for three enzymes and as the product of at least four reactions in the pathway of oligosaccharide-lipid synthesis. The numerous interconversions among the dolichyl phosphate forms are explained in this review. Finally, differences in the regulation of this pathway between tissues and cultured cells are discussed.
