section 16.1

Biosynthesis of Glycoproteins

313

RER

FIG URE 16-7

Proposed pathway for the biosynthesis of Asn-linked glycoproteins, including phosphorylation of high-mannose

structures on glycoproteins destined for inclusion in lysosomes. Glycosylation begins during protein synthesis in the

rough endoplasmic reticulum. Transfer of glycoproteins between subcellular compartments is thought to be

accomplished by vesicle transport. Nucleotide sugars must enter the Golgi cisternae from their site of synthesis in the

cytosol. Completed glycoproteins leave the trans Golgi for their ultimate intra- or extracellular destinations in membrane

vesicles. The enzymes catalyzing the numbered reactions are (1) oligosaccharyltransferase, (2) a-glucosidase I;

(3) «-glucosidase II, (4) endoplasmic reticulum a-l,2-mannosidase, (5) Golgi ar-mannosidase I,

(

6

) N-acetylglucoaminyltransferase I, (7) Golgi œ-mannosidase II, (

8

) N-acetylglucosaminyltransferase II,

(9) fucosyltransferase, (10) galactosyltransférase, (11) sialyltransferase, (I) N-acetylglucosaminylphosphotransferase,

(II) N-acetylglucosamine-1-phosphodiesterœ-N-acetylglucosaminidase. [Reproduced with permission from R. Komfeld

and S. Kornfeld, Assembly of asparagine-linked oligosaccharides.

A n n u . Rev. B iochem .

54:631 (1985). © 1985 by

Annual Reviews Inc.]

to dolichol phosphate. The final chain contains nine man-

nose, two GlcNAc, and three glucose residues attached

to a dolichol chain through a diphosphate linkage. A

scheme for the addition of these sugars is shown in

Figure 16-8. The dolichol phosphate is located in the

rough endoplasmic reticulum, with the phosphate prob-

ably oriented toward the cytosol. The first two GlcNAc

and five mannose residues that are attached to dolichol

are derived from UDP-GlcNAc and GDP-mannose, re-

spectively. Their addition occurs on the cytoplasmic face

of the rough endoplasmic reticulum. The oligosaccharide-

dolichol is then translocated from the cytoplasmic to the

luminal side of the membrane. Further attachment of four

mannose and three glucose residues occurs within the