318
chapter 16
Carbohydrate Metabolism III: Glycoproteins, Glycolipids, GPI Anchors, Proteoglycans, and Peptidoglycans
GIcNAc
I (36
-
Fuca2GaI|33GaINAc-
t
9
GIcNAc
IP6
♦
Gai|33GaINAc-
GIcNAc
I P6
GlcNAcp3Gaip3GalNAc-
A, B blood g ro u p s
Î
Fuca2Gaip3GalNAc-
m
■
Gaip3GalNAc- -
co re 1
-
GlcNAcp3GaIp3GalNAc-
I
SA
| a6
Fuca2Gaip3GaINAc-
|g
1
SA
| a6
Galp3GalNAc-
SA3GaIp3GaINAc- •
GIcNAc
|P6
GlcNAcP3Gaip3GaINAc-
SA
| a6
SAa3 Gaip3GalNAc-
FIGURE 16-11
Processing reactions of O-glycan core 1: (a) core 2 /T6-GlcNAc-T; (b) elongation /33-GIcNAc-T; (c) I /66-GlcNAc-T;
(d) a6-SA-T I; (e) «3-SA-T; (f) «6-SA-T II; (g) a2-Fuc-T. [Reproduced with permission from I. Brockhausen,
Clinical aspects of glycoprotein biosynthesis.
C rit. Rev. C lin. Lab. Sci.
30:80 (1993).]
on O-glycans on Gal, GIcNAc, or GalNAc at various
positions.
Another interesting O-glycosylation type which may
be related to cellular regulation is the attachment of sin-
gle O-GlcNAc to specific Ser or Thr on many cytoplas-
mic and nuclear proteins. The O-glycosylating GlcNAcT
is a unique, highly conserved 110 kDA catalytic sub-
unit that is trimerized when active. In contrast to other
glycosyltransferases involved in synthesis of O-glycans,
this GlcNAcT has cytosolic and nuclear localization. All
O-GlcNAc modified proteins to date also occur as phos-
phorylated proteins, and protein phosphorylation and
O-GlcNAc modification appear to be reciprocal and
their interrelationship complex.
There are important
implications that O-GlcNAc glycosylation may play a role
in disease processes. The alpha toxin of
Clostridium novyi
(the gangrene-causing bacteria) is an O-GlcNAcT that is
toxic due to its glycosylation of Rho subfamily proteins. In
Alzheimer’s disease, Tau microtubule-associated protein
is hyperphosphorylated, whereas in unaffected brain, Tau
is repeatedly O-GlcNAc modified.
Biosynthesis of GPI-Anchored Proteins
The synthesis of glycosylphosphatidylinositol (GPI) an-
chors of proteins, including Thy-1 of neurons and lym-
phocytes, is primarily carried out within the lumen
of the rough endoplasmic reticulum. The anchor con-
sists of a phosphatidylinositol-glucosamine-mannose
3
-
ethanolamine
phosphate
core
that
is
linked
to
the
a-carboxyl of the carboxyterminal amino acid of a protein
(Figure 16-12). This addition takes place within minutes of
Protein—c n h c h 2c h 2—o
I
[Mannose]
o
/
FIGURE 16-12
A typical GPI-anchor structure in human erythrocytes. GalNAc means
N-acetyl galactosamine. Waved lines indicate alkyl chains. [Reproduced
with permission from M. Tomita, Biochemical background of paroxysmal
nocturnal hemoglobinuria.
B io ch em . B iophys. A c ta
1455, 269 (1999).]
