section 16.1
Biosynthesis of Glycoproteins
FIGURE 16-14
Structure of ganglioside Gmi ■
Ceramide portion of a representative
ganglioside is shown beneath dashed line. Ceramide is synthesized by a
condensation of serine (boldface) with palmitoyl-CoA followed by an
N-acylation. Ceramide is then glycosylated stepwise to produce a
glycosphingolipid, such as the ganglioside
shown here.
[Reproduced with permission from C. B. Zeller and R. B. Marchase,
Gangliosides as modulators of cell function.
A m . J. P h ysio l.
FIGURE 16-15
Comparison of topography of glycosphingolipid and N-linked
glycoprotein glycosylation reactions. Approximate topographies
of major glycosylation reactions important to ganglioside synthesis
are depicted at left and those pertaining to N-linked glycosylation of
glycoproteins at right. Distributions of glycosphingolipid
glycosyltransferases are much less well defined than are their
glycoprotein counterparts. [Reproduced with permission from
C. B. Zeller and R. B. Marchase, Gangliosides as modulators of cell
A m . J. P h ysio l.
262:0344 (1992).]
on glycolipids and glycoproteins. In particular, some can-
cer cells end up with oligosaccharide structures identical
to those used by normal leucocytes to attach to blood ves-
sel receptors (selectins) for invasion of tissues; unfortu-
nately, in cancer cells this change promotes metastasis.
The expression of new terminal carbohydrate structures
by cancer cells can be prognostic as to disease outcome.
For example, patients with either
colorectal (Dukes C
breast carcinoma
that did not express sialosyl-
GalNAc-(sialosyl-Tn antigen) terminal disaccharides had
a much better survival rate than patients positive for this
antigen. Many of these carbohydrate structures can oc-
cur as terminal sequences on either glycolipids or gly-
coproteins. It is interesting that drugs (cyclosporin A,
tamoxifen, and verapamil) that reverse multidrug resis-
tance inhibit ceramide glucosylation and, thereby, GSL
Glyceride glycolipids have been reported. Monogalac-
0.5% of the total lipid of adult nervous tissue and
occurs in kidneys but not elsewhere. MGD and di-
galactosyldiacylglycerol (DGD) increase in concentra-
tion during myelination. Sulfated forms of diacylglycero-
and alkylacylglycerogalactolipid make up about 2-7%
of rat brain sulfolipids. Sulfoalkylacylglycerogalactolipid
(“seminolipid”) is the major sulfolipid of mammalian
sperm and testes. An elevated concentration of semino-
lipid occurs in the primary spermatocyte stage of sperm
development and is correlated with a rise in galactolipid
sulfotransferase activity.
Breakdown of GSL occurs in the lysosomes, and in-
herited deficiencies of lysosomal hydrolases or of sphin-
golipid activator proteins (SAPs, saposins) can give rise
to sphingolipid storage diseases. The SAPs are necessary
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