section 16.1
Biosynthesis of Glycoproteins
311
o
A
UDP-GIcNAc
UDP-Gal
UDP-GIcUA
UDP-GalNAc
UDP-Xylose
CMP-Sialic acid
GDP-Fucose
GDP-Mannose
OH
OH
Uridine diphosphate glucose (UDP-giucose)
FIGURE 16-4
Examples of nucleotide sugars involved in glycoconjugate biosynthesis.
The structures of these compounds are the same as that of UDP-glucose
but with different nucleotides and sugars.
nasal bridge, protruding tongue, prominent mandible, and
a narrow or high-arched palate). The reduced fucosy-
lation is most likely due either to a failure of fucose
transport into the Golgi apparatus or in the synthetic
pathway of fucose. Loss of fucosylation results in poor
adhesion of leucocyte selectin receptors to endothelial cell
oligosaccharides.
16.1
Biosynthesis of Glycoproteins
Glycoproteins can be classified into two major types
with
differing
biosynthetic
pathways.
The
first
is
the asparagine-linked glycoproteins (
N-glycans
), which
contain
an
N-glycosidic
linkage
between
N-acetyl-
glucosamine and the /1-amide nitrogen of an asparagine
residue in the protein (abbreviated GlcNAc-N-Asn). This
type of linkage predominates in serum glycoproteins.
The second is the serine (threonine)-linked glycopro-
tein (
O-glycans
), such as salivary mucin and a number
of other proteins and proteoglycans, which contain an
O-glycosidic linkage between the hydroxyl groups of ser-
ine or threonine and N-acetylgalactosamine (abbreviated
GalNAc-O-Ser/Thr). Details of monosaccharide units and
linkages are usually indicated by structures of the kind
shown in Figure 16-1.
Fructose
_
6
-phosphate
/
6
lu-
\
ta -
N H jj
Vm ine
J
G luco sam in e „
6
-phosp hate
N -A cetylglucosam ine _
6
-phosp hate
"
N -A cetylglucosam ine
1
-phosphate
N -A cetylgalactosam ine
1
-phosphate
UD P-glucuronic
|UD P-lduronic
_____ acid______
1
acid
jU P P -g iu c o s e !
|UD P-xylose]-
♦lU D P -arabin osel
.
M annose
6
-phosphate
M an n o se .
1
-phosphate
U D P -g alacto se
gVucose
) U T P
G alacto se
1
-phosphate
G alactose
-----------*IG D P-m annosel—
r G lucosam ine
_
N -A cetyl-
'g lu co s am in e
N -A cetyi-
m annosam ine :
'd eo xym an n o se
iGDP-<uçosë]
Fucose
1
-phosphate
Fucose
N -A cetylm ann osam ine
'
6
-phosphate
N-A cetylneuram inic acid
9-phosphate
N -A cetylneuram inic acid
G alactosam ine
C M P -N -a c e ty l-
neuram inic acid
FIGURE 16-5
Biosynthetic pathways for nucleotide sugars. [Reproduced with permission from H. Schächter, Glycoprotein
biosynthesis. In:
T h e G lyco co n ju g a tes,
Vol. 2, M.I. Horowitz and W. Pigman (Eds). Academic Press,
San Diego, 1977.]
