chapter 16
Carbohydrate Metabolism III: Glycoproteins, Glycolipids, GPI Anchors, Proteoglycans, and Peptidoglycans
C H ,
I 3
j 3
H — (C H ;— C = C H — C H ) — C H ,— C H — C H .— C H ,— o —
P — O H
Dolichol phosphate
N-Acetylglucosam inyldiphosphoryldolichol
M annosylphosphoryldolichol
Structures of dolichol phosphate, GlcNAc-P-P-Dol, and Man-P-Dol. GlcNAc-P-P-Dol is the first compound
formed in the biosynthesis of the lipid-linked oligosaccharide shown in Figure 16-5. Replacement of GlcNAc by
-OH in GlcNAc-P-P-Dol yields dolichol diphosphate (dolichol pyrophosphate). Replacement of Man by Glc in
Man-P-Dol yields Glc-P-Dol.
N-Glycan Asn-Linked Glycoproteins
The discovery that dolichol phosphates and pyrophos-
phates (diphosphates) are carriers for oligosaccharides
in eukaryotic cells initiated the modem era of glycopro-
tein biochemistry. These lipid-linked oligosaccharides
are precursors for the carbohydrate side chains of the
asparagine-linked glycoproteins. Because of this common
precursor, all of the side chains of these glycoproteins
share the same carbohydrate core, shown within the
dashed box in Figure 16-la.
are a family of long-chain polyisoprenols
that occur only in eukaryotes. They are related in struc-
ture and function to undecaprenyl phosphate, a prokary-
otic polyisoprenol used in the synthesis of peptido-
glycan (see below). Dolichols contain 65-110 carbons
arranged as
13-22 isoprene units, two in the trans
configuration, the remainder in the cis configuration.
The initial isoprene unit is saturated and carries a hy-
droxyl group, which is esterified with orthophosphoric
(monophosphoric) or pyrophosphoric (diphosphoric) acid
in dolichol phosphate and pyrophosphate, respectively
(Figure 16-6).
The pathway for
de novo
synthesis of dolichol phos-
phate is the same as for cholesterol until production
of famesyl pyrophosphate (Chapter 19). Two salvage
pathways provide for the reutilization of dolichol and
dolichol pyrophosphate once transfer of oligosaccharide
from the dolichol to glycoprotein has occurred. A sig-
nificant portion of the dolichol in liver is present as the
free alcohol or as a fatty acid ester, and dolichol ab-
sorbed from the diet may enter this pool. Phosphory-
lation of dolichol is catalyzed by a dolichol kinase via
cytidine triphosphate (CTP). Removal of one phosphate
also permits recycling of the dolichol pyrophosphate re-
leased by transfer of the oligosaccharide to a protein
Biosynthesis of an asparagine-linked oligosaccharide
chain proceeds in three steps. A lipid-linked oligosaccha-
ride precursor is first synthesized and then transferred
to an available asparagine residue, in a nascent or
newly completed polypeptide chain. Synthesis and trans-
fer together make up the initiation step. After transfer,
several sugar residues are removed from the oligosaccha-
ride (the processing step), following which the peripheral
sugars of the mature glycoprotein are added (the elonga-
tion step). If all steps proceed normally, the mature side
chain is of the “complex” type. Glycoproteins with par-
tially processed side chains may also be released. If they
contain none of the peripheral sugars, they are termed
“high-mannose” oligosaccharides. “Hybrid” oligosaccha-
rides have features of both high-mannose and complex
The above steps, not including synthesis of the lipid-
linked oligosaccharide, are outlined in Figure 16-7. Struc-
tures of the side chains of mature glycoproteins depend
on the specificities of the processing and elongation en-
zymes (glycosidases and transferases, respectively) and
on the order in which they function. Regulatory steps
may occur in this pathway, but their function is poorly
) Initiation
includes synthesis of the oligosaccharide-
lipid precursor and transfer of the oligosaccharide to a
protein. Evidence for a possible role for retinol (vitamin A)
as a carrier in this step is discussed in Chapter 38.
The lipid-oligosaccharide is built by sequential attach-
ment of mannose, N-acetylglucosamine, and glucose units
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