Chemistry Reference
In-Depth Information
11.1.2
Biosynthesis
The formation of the core protein of the PGs is the fi rst step in this process and
proceeds according to the general mechanisms of protein biosynthesis. The molec-
ular size of the individual protein core varies over a broad range from 20 up to
400 kDa (Table 11.1). The GAG chain is synthesized by a posttranslational modi-
fi cation of the protein. The carbohydrate-protein linkage region (Figure 11.1) is
assembled by the sequential action of UDP- xylosyltransferase, UDP - galactosyl-
transferase and UDP-glucuronyltransferase. Polymerization of the GAG chain
then results from the concerted action of glycosyltransferases (
N
- acetylgalactos-
aminyltransferase,
N
- acetylglucosaminyltransferase, glucuronyltranferase and
-
galactosyltransferase). Different GAG protein-binding regions are synthesized for
KS I and II (see Figure 11.1). Substrates of the glycosyltransferases are nucleotide
(UDP)-activated monosaccharides imported from the cytoplasm which are trans-
ferred to an appropriate acceptor which is either the nonreducing end of a growing
GAG chain or an amino acid residue of a polypeptide chain. Epimerization of GlcA
to IdoA is coupled with the process of sulfation and occurs along chain elongation.
The sulfate donor in this reaction is 3
β
- phosphosulfate,
which is formed from ATP and sulfate in two steps. A single enzyme is respon-
sible for removal of the
N
-acetyl moiety of the glucosamine residue (HS) and its
′
- phosphoadenosine - 5
′
Table 11.1
Main PGs in multicellular organisms (acronyms and chromosomal location refer to human genes).
PG location
PG type
Acronym
(access to
gene bank)
MW (kDa)
core protein
GAG chain
Chromosomal
location
Type
Number
Extracellular
HA - binding
Aggrecan
ACAN
210 - 250
CS/KS
>
100/
>
30
15q26.1
Brevican
BCAN
145
CS
0 - 3
1q31
Neurocan
NCAN
136
CS
1
19q12
Versican
VCAN
260
CS
15 - 17
5q14.3
Extracellular
Leucine - rich
Biglycan
BCN
38
DC
2
Xq28
Decorin
DCN
36
DC
1
20q21.33
Fibromodulin
FMOD
42
KS
4
1q32
Lumican
LUM
38
KS
4
12q21.3
Basement membrane
Agrin
AGRN
215
HS
2
1p36.33
Collagen XVIII
COL - 18A1
2451 aa
a
HS
2
21q22.3
Perlecan
HSPG2
450
HS
3
1p36.1 - 3
Cell surface
Syndecan - 1
SDC1
32
HS/CS
3/2
2p24.1
Syndecan - 2
SDC2
22
HS
3
8q22 - 23
Syndecan - 3
SDC3
46
HS/CS
4/2
1p22.3
Syndecan - 4
SDC4
35
HS/CS
3/1
20q12
Glypican 1 - 6
GPC1 - 6
59 - 65
HS
2 - 5
see Text
a
Number of amino acids.
