section 16.1
Biosynthesis of Glycoproteins
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,
) N-acetylglucoaminyltransferase I, (7) Golgi œ-mannosidase II, (
) 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
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