Carbohydrate Metabolism III:
Glycoproteins, Glycolipids,
GPI Anchors, Proteoglycans,
and Peptidoglycans
Glycoconjugates are composed of linear and branching
arrays of sugars attached to polypeptide or lipid back-
bones. They include glycoproteins, glycosphingolipids,
glycosylphosphatidyl inositol (GPI), glycosaminoglycans
(together with proteoglycans), and peptidoglycans.
Most of the biosynthetic pathways for oligosaccharide
chains have been determined within the last decade and
genes for a number of the enzymes in these pathways have
been isolated and sequenced. Better methods for substrate
and product identification have also improved understand-
ing of the details in specific reactions. It is important to
understand that many factors and pathways come into play
within specific membrane compartments for proper gly-
cosylation to occur. Because so many functions, including
proper folding, intracellular routing of glycoproteins, and
cellular recognition, are ascribed to oligosaccharides, mis-
takes in synthesis may result in various syndromes. Con-
versely, altered oligosaccharide biosynthesis may occur as
a result of disease states that hamper appropriate glyco-
sylation. This may lead to further complications such as
a change in blood type, which is based on the presence
of specific terminal sugars on red blood cells (RBCs) and
other cells.
The elaboration of oligosaccharide chains occurs at
specific sites in all cells. In prokaryotes, the enzymes are
located on the plasma membrane, whereas in eukaryotes,
they occur predominantly on membranes of the endoplas-
mic reticulum and Golgi apparatus. The reactions require
energy in the form of a nucleotide-sugar donor molecule.
This use of nucleotides as carriers is similar to that seen in
the synthesis of phospholipids (Chapter 19) and glycogen
(Chapter 15). Transfer of the sugar portions of the donors
to acceptor molecules is catalyzed by glycosyltransferases.
The general reaction is summarized below.
XDP-sugar (A) + sugar (B) • • • (C)
(A)-O-(B) • • ■
(C) + XDP
In this reaction, XDP-sugar (A) is the nucleoside diphos-
phate sugar donor, and sugar (B)- • -(C) is the acceptor,
usually an oligosaccharide attached to a protein or lipid
(C). In the product (A)-O-(B)- ■
-(C), the sugar from the
donor (A) is linked to the terminal sugar (B) on the accep-
tor by the glycosidic bond. Energy to form the glycosidic
bond is provided by the phosphate ester linkage between
the sugar and the nucleoside diphosphate. Dolichol phos-
phate and dolichol pyrophosphate are intermediate sugar
carriers in the synthesis of asparagine-linked glycopro-
teins. The topography of glycosylation reactions is im-
portant, with some transferase reactions, such as dolichol-
oligosaccharide synthesis, occurring on the cytoplasmic
membrane face and the majority of other reactions taking
place within the lumen of either the endoplasmic reticulum
or Golgi apparatus.
Assembly of an oligosaccharide having 10 or more
sugars may require almost the same number of glyco-
syltransferases, since each enzyme is usually specific for
the formation of one glycosidic bond between a particular
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