chapter 16
Carbohydrate Metabolism III: Glycoproteins, Glycolipids, GPI Anchors, Proteoglycans, and Peptidoglycans
in the biochemistry of GPI anchors may lead to novel
therapeutic agents to fight infections and possibly other
Biosynthesis of Glycosphingolipids
The glycosphingolipids (GSLs, glycolipids) include neu-
tral glycosphingolipids, gangliosides,
and sulfatogly-
cosphingolipids. The terms “cerebroside” and “ganglio-
side” reflect their abundance in gray and white matter of
the central nervous system. Glycolipids are widely dis-
tributed in the body. Gangliosides
and GTib have
been found to enhance the effect of nerve growth fac-
tor (NGF) on neurite outgrowth. Such studies may lead
to effective treatments after spinal cord injury. Ganglio-
sides also are known to modulate protein kinase and
NGF receptor function. All glycosphingolipids contain an
oligosaccharide chain of one or more residues of galactose,
glucose, N-acetylglucosamine, N-acetylgalactosamine, or
fucose. Gangliosides also have one or more residues of
sialic acid, whereas the sulfatoglycosphingolipids con-
tain sulfate groups in ester linkage on some residues.
Structures of the glycosphingolipids are presented in
Chapter 10.
GSLs are classified by the sequence and type of the
first four sugars attached to ceramide (Table 16-1). The
prefixes used to indicate the core structure are listed in
Table 16-1, along with the tissue in which the different
types are predominantly found. This system reflects the
synthetic history of a structure and is useful for under-
standing biosynthetic pathways. Structures of the three
most abundant glycolipids and the tissues in which they
occur are shown in Table 16-1.
GSLs of the ganglio- series are designated by the
capital letter G and the sialic acid content is desig-
nated by a subscripted capital letter (A = asialo; M =
monosialo; D = disialo; etc.). The length of the neu-
tral sugar chain is designated by a subscripted number
using the formula (5 —
equals the number
of neutral sugars in the ganglioside. Further designa-
tions of
or /3 relate to the positioning of the sialic
acid. Using this nomenclature, Gmi is a ganglioside con-
taining one sialic acid and four neutral sugars (Figure
16-14). The initial glucosylation of ceramide occurs on
the cytoplasmic side of the Golgi while subsequent step-
wise sugar transfers occur within the Golgi lumen and
may result in 300-400 possible GSL types in differ-
ent cells. Subcellular fractionation and drug studies that
disrupt Golgi function have suggested that the distribu-
tion of glycosyltransferases synthesizing GSLs may differ
from enzymes involved in N-linked glycoprotein synthesis
(Figure 16-15).
During the progression of cancer, many changes in gly-
cosyltransferases result in alteration of oligosaccharides
TABLE 16-1
N a m es, S tru ctu res, a n d M a jo r T issue D istrib u tio n s o f O lig o sa cch a rid es F o u n d in G lyco lip id s
Gal/31 —>3GlcNAcß 1
Central nervous system
Gal/31 ->4GlcNAc /31 ^3Gal/31 -^4Glc/31 -ACer
Central nervous system, blood
group antigens
Gal/31 —>3Gal/31
1 -a4G1c/31 -ACer
Gala (GL
(GalNAc? 1 —>3Gal?l)—>4Galotl ->4Gal/31 -ACer
Central nervous system, kidney
Globo (GL4a)
GalNAc? 1 —>3Gala 1
1 -a4G1c/31 -ACer
Kidney, heart, erythrocytes
Ganglio (GM1)
Gal/31 —>3GalNAc/3l ^4Gal/31 -a4G1c/3 1
^ C er
Central nervous system
Lactosyl ceramide (GL
Gal/31 -a4G1c/31 —>Cer
Major glycolipid in most
non-neural tissue
Glucosyl ceramide (GLia)
Major neutral glycolipid in
central nervous system
Galactosyl ceramide (GLp,)
Major neutral glycolipid in plasma
*The names on the first six lines are the prefixes used to designate the core sugars when naming glycolipids. For all the structures, the names in
parentheses are the old designations for the corresponding glycosylceramide. The only exception is GL2b, which stands for Gal-Gal-Cer, not for the
Gala tetrasaccharide.
tAlthough the Gala structure is shown as a tetrasaccharide, no Gala-type glycolipids having structures more complex than Gal-Gal-Cer (galabiosyl-
ceramide) have been purified from natural sources. Gal= Galactose, Glc = glucose, GalNAc = N-acetylgalactosamine, Cer = ceramide.
fThe tissues listed in this column are those in which relatively large amounts of glycolipid having the indicated structure are found. Many of these
compounds are also found in other tissues at lower concentrations.
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