Author: Gianpiero Pescarmona
The topology of N-linked oligosaccharide biosynthesis involves enzymatic reactions on both sides of the ER membrane. Monosaccharides from UDP-GlcNAc and GDP-Man, synthesized in the cytoplasm, are transferred in an ordered, stepwise fashion to the lipid carrier dolichyl phosphate. This phase of biosynthesis pathway results in the Man5GlcNAc2branched oligosaccharide. The dolichol anchored heptasaccharide is flipped into the ER lumen where Man-P-Dol and Glc-P-Dol dependent monosaccharide transferases extend the oligosaccharide to Glc3Man9GlcNAc2. This oligosaccharide is transferred to proteins. Man-P-Dol and Glc-P-Dol are synthesized on the cytosolic side or the membrane and must be translocated into the ER. In addition to its use in N-linked protein glycosylation Man-P-Dol is required for GPI-anchors and O-mannosylation.
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