The synthesis of chondroitin sulphate in vertebrates begins with the transfer of a xylose residue from UDP-xylose to a particular serine residue of the protein component; finally, two galactose residues and glucuronic acid or, alternatively
N-acetylgalactosamine are added [255]. Heparin
and heparan sulphate are also bound to serine via
the same trisaccharide as that which binds chondroitin sulphate (Fig. 13.13). A glycopeptide with
galactose, xylose and serine has also been isolated from the glycosaminoglycan of Loligo pealei
[123]; unfortunately, there is almost no information about the biosynthetic routes leading to the
mucopolysaccharides of the invertebrates or
about the structure of their protein bonds. Epimerization of part of the n-glucuronic acid residues to L-iduronic acid, and the O-sulphation on
C-4 or C-6 of the galactosamine, or on C-2 or C-3
of iduronic acid, takes place after polymerization.
There is usually one sulphate per disaccharide,
but over- or under-sulphated chondroitin sulphate
is also found. The mucopolysaccharides even of
one tissue are heterogeneous in the number and
position of sulphate and iduronic acid residues.
According to the usual nomenclature, C-4 sulphated polysaccharides are referred to as chondroitin A, and C-6 sulphated polysaccharides as
chondroitin C. However, there are frequently
hybrid molecules with sulphate groups at both
positions. Polysaccharides with a high proportion
of iduronic acid are known as chondroitin B or
dermatan sulphate; in this case, the remaining
glucuronic acid residues are concentrated on the
chain in one or two clusters [115]. As epimerization and sulphation occur after polymerization,
proteoglycans with the same primary structure
and the same protein components may bear different names. It would be preferable to refer to
all as chondroitin sulphate, referring at the same
time to the proportion of iduronic acid residues
and C-4 or C-6 sulphate groups [115].
Chondroitin sulphate is considered as oversulphated when it includes bi- or even trisulphated disaccharide units, i.e. when there is, on
average, more than one sulphate residue per disaccharide. The localization of the extra sulphate
residues varies with the species. In chondroitin
sulphate D from elasmobranch cartilage and in
chondroitin sulphate K from the gill cartilage of
the xiphosuran Tachypleus tridentatus, both the
N-acetylgalactosamine and the glucuronic acid
residue bear one sulphate residue. In the chondroitin E of the cranial cartilage of the cephalopods Loligo sp. and Ommastrephes sloani, about
half the N-acetylgalactosamine residues are 4,613.4.1 Glycosaminoglycans
483
bissulphated; the rest are C-4 sulphated and C-6
glucose substituted (Fig.13.13) [124]. The Nacetylgalactosamine residues of the chondroitin
sulphate from the chorda dorsalis of the agnathan
Myxine glutinosa are 4,6,-bissulphated; the dermatan sulphate in the skin of Myxine and the
related genus Eptatretus contains trissulphated
subunits, in which the uronic acid is 2- or
3-sulphated and the galactosamine 2,6bissulphated. Unlike in Myxine, the skin and
chorda of the acranian Branchiostoma lanceolatum have normal dermatan sulphate, and not
over-sulphated chondroitin sulphate. Cephalopod
cartilage contains several proteoglycans with
molecular masses between 0.6 and 1.3 MDa;
these bear two to five over-sulphated chondroitin
sulphate chains, and differ in both the content of
hexuronic acid and sulphate groups and the size
of the core proteins. These proteoglycans are also
unable to integrate in vitro with hyaluronic acid
[144, 283]. In addition to typical chondroitin sulphates, the body wall of some holothurians has
been found to contain rather unusual fucosecontaining glycosaminoglycans [145, 279]. In one
such glycosaminoglycan from Ludwigothurea grisea, part of the N-acetylgalactosamine residues
are 4,6-bissulphated; the 3-hydroxyl of the glucuronic acid residues bear either sulphate or a
sulphated fucose disaccharide and they are,
therefore, resistant to chondroitinase. The fucose
chain has the structure Fuc(3,4-Sf2)a(1-2)Fuc
(4-St)a(1-3)G1cUA- [279]. However, over-sulphated chondroitin sulphate is found in the cartilage lying at the base of the tentacles of the polychaete Eudistilia polymorpha. The eggs of the
gastropod Pomacea sp. contain the typical heparan sulphate and acidic galactans, as well as
chondroitin sulphate residues which, however,
are never C-6 sulphated and have no iduronic
acid residues [134]. The skin of the cephalopod
Ommastrephes contains sulphate-free chondroitin; in vertebrates this is found only in the cornea
of the eye [123, 144].
Heparin is synthesized and stored in the mast
cells of the connective tissues. Its clottinginhibitory properties are well known; they arise
from the fact that the inactivation of thrombin by
antithrombin III is increased manyfold when
thrombin and antithrombin are bound to the
same heparin chain. Heparan sulphate, as a
widely found component of the cell surface, is
very different to heparin in function but the two
are structurally very difficult to distinguish. Both
substances show great similarity to chondroitin
sulphate in their biosynthesis and the structure of
N-acetylgalactosamine are added [255]. Heparin
and heparan sulphate are also bound to serine via
the same trisaccharide as that which binds chondroitin sulphate (Fig. 13.13). A glycopeptide with
galactose, xylose and serine has also been isolated from the glycosaminoglycan of Loligo pealei
[123]; unfortunately, there is almost no information about the biosynthetic routes leading to the
mucopolysaccharides of the invertebrates or
about the structure of their protein bonds. Epimerization of part of the n-glucuronic acid residues to L-iduronic acid, and the O-sulphation on
C-4 or C-6 of the galactosamine, or on C-2 or C-3
of iduronic acid, takes place after polymerization.
There is usually one sulphate per disaccharide,
but over- or under-sulphated chondroitin sulphate
is also found. The mucopolysaccharides even of
one tissue are heterogeneous in the number and
position of sulphate and iduronic acid residues.
According to the usual nomenclature, C-4 sulphated polysaccharides are referred to as chondroitin A, and C-6 sulphated polysaccharides as
chondroitin C. However, there are frequently
hybrid molecules with sulphate groups at both
positions. Polysaccharides with a high proportion
of iduronic acid are known as chondroitin B or
dermatan sulphate; in this case, the remaining
glucuronic acid residues are concentrated on the
chain in one or two clusters [115]. As epimerization and sulphation occur after polymerization,
proteoglycans with the same primary structure
and the same protein components may bear different names. It would be preferable to refer to
all as chondroitin sulphate, referring at the same
time to the proportion of iduronic acid residues
and C-4 or C-6 sulphate groups [115].
Chondroitin sulphate is considered as oversulphated when it includes bi- or even trisulphated disaccharide units, i.e. when there is, on
average, more than one sulphate residue per disaccharide. The localization of the extra sulphate
residues varies with the species. In chondroitin
sulphate D from elasmobranch cartilage and in
chondroitin sulphate K from the gill cartilage of
the xiphosuran Tachypleus tridentatus, both the
N-acetylgalactosamine and the glucuronic acid
residue bear one sulphate residue. In the chondroitin E of the cranial cartilage of the cephalopods Loligo sp. and Ommastrephes sloani, about
half the N-acetylgalactosamine residues are 4,613.4.1 Glycosaminoglycans
483
bissulphated; the rest are C-4 sulphated and C-6
glucose substituted (Fig.13.13) [124]. The Nacetylgalactosamine residues of the chondroitin
sulphate from the chorda dorsalis of the agnathan
Myxine glutinosa are 4,6,-bissulphated; the dermatan sulphate in the skin of Myxine and the
related genus Eptatretus contains trissulphated
subunits, in which the uronic acid is 2- or
3-sulphated and the galactosamine 2,6bissulphated. Unlike in Myxine, the skin and
chorda of the acranian Branchiostoma lanceolatum have normal dermatan sulphate, and not
over-sulphated chondroitin sulphate. Cephalopod
cartilage contains several proteoglycans with
molecular masses between 0.6 and 1.3 MDa;
these bear two to five over-sulphated chondroitin
sulphate chains, and differ in both the content of
hexuronic acid and sulphate groups and the size
of the core proteins. These proteoglycans are also
unable to integrate in vitro with hyaluronic acid
[144, 283]. In addition to typical chondroitin sulphates, the body wall of some holothurians has
been found to contain rather unusual fucosecontaining glycosaminoglycans [145, 279]. In one
such glycosaminoglycan from Ludwigothurea grisea, part of the N-acetylgalactosamine residues
are 4,6-bissulphated; the 3-hydroxyl of the glucuronic acid residues bear either sulphate or a
sulphated fucose disaccharide and they are,
therefore, resistant to chondroitinase. The fucose
chain has the structure Fuc(3,4-Sf2)a(1-2)Fuc
(4-St)a(1-3)G1cUA- [279]. However, over-sulphated chondroitin sulphate is found in the cartilage lying at the base of the tentacles of the polychaete Eudistilia polymorpha. The eggs of the
gastropod Pomacea sp. contain the typical heparan sulphate and acidic galactans, as well as
chondroitin sulphate residues which, however,
are never C-6 sulphated and have no iduronic
acid residues [134]. The skin of the cephalopod
Ommastrephes contains sulphate-free chondroitin; in vertebrates this is found only in the cornea
of the eye [123, 144].
Heparin is synthesized and stored in the mast
cells of the connective tissues. Its clottinginhibitory properties are well known; they arise
from the fact that the inactivation of thrombin by
antithrombin III is increased manyfold when
thrombin and antithrombin are bound to the
same heparin chain. Heparan sulphate, as a
widely found component of the cell surface, is
very different to heparin in function but the two
are structurally very difficult to distinguish. Both
substances show great similarity to chondroitin
sulphate in their biosynthesis and the structure of