484
13 The Structure and Metabolism of Carbohydrates
their protein bonds. These polysaccharides are
also highly modified after their biosynthesis; the
resulting variability of the heparins is even
greater than that of the other glycosaminoglycans. The different heparin variants vary greatly
in their clotting-inhibitory activity in proportion
to the content of an oligosaccharide sequence
necessary for antithrombin binding [118].
A typical heparin has 70-90 % iduronic acid;
most glucosamine residues are N-sulphated and
only a few carry N-acetyl groups. The C-6, and
often the C-3, of the glucosamine is O-sulphated,
as is sometimes the C-2 of many of the iduronic
acids, but never glucuronic acid. Most of the
heparins have a molecular mass of 5-15 kDa;
individual chains carry galactose, xylose and
serine as components of a protein bond. Thus,
heparin is apparently synthesized as a proteoglycan and only later separated from the protein. A
"macromolecular" heparin of 1 MDa, isolated
from rat skin, has several polysaccharide chains
of 60-100 kDa and these sit on a protein component of very unusual amino acid composition: this
consists only of serine, glycosylserine and glycine
and is protease resistant. Heparan sulphate
appears to be a somewhat modified form of heparin but it is probably more correctly looked upon
as an independent family of the glycosaminoglycans [89]; it has no clotting-inhibitory activity.
Only a few glucosamine residues are deacetylated
and can thus be N-sulphated; because of the
specificity of the corresponding enzyme, this
lower N-sulphation leads to a reduction in the
epimerization of glucuronic acid to iduronic acid
[273].
Heparin is thought to be absent from the lower
vertebrates; it has been sought without success in
the lamprey Petromyzon marinus, the shark
Squalus acanthias and the teleosts Sebastes marinus and Cyprinus carpio [120]. As the quantity of
clotting-active heparins is relatively low in mammalian organs, a practical source for this substance was sought amongst the invertebrates. In
fact, the mussels Spisula solidissima, Cypridina
islandica, Anomalocardia brasiliana and Tivela
mactroides contain considerable amounts of
heparin-like polysaccharides which have a large
proportion of antithrombin-binding sequences
and a corresponding clotting-inhibitory activity.
The glycosaminoglycan from C. islandica is
known as mactin [210]. An unusual heparin sulphate with many sulphate groups, little iduronic acid
and low clotting-inhibitory activity has been isolated from the lobster; most of the disaccharides
in this case consist of glucuronic acid and
glucosamine-N,O-bissulphate, whilst the nonsulphated or mono-sulphated units of the typical
vertebrate heparan sulphate are rare [120].
In vertebrates, there are two types of proteoglycan with the repetitive sequence of keratan
sulphate (Fig. 13.13). Type I from the cornea has
a molecular mass of about 80 kDa and contains
one to three polysaccharide chains bound
N-glycosidically to asparagine via N-acetylglucosamine. Such a bond has also been found
in a keratan sulphate from the skin of the teleost
Scomber japonicus. This type of carbohydrateprotein bonding is typical of glycoproteins which
arise by the transfer of a dolichol-bound oligosaccharide to an asparagine residue. Type-II keratan
sulphate is present in various connective tissues
and is bound O-glycosidically via N-acetylgalactosamine to serine or threonine. The binding
N-acetylgalactosamine residue is commonly substituted by N-acetylglucosamine or sialylgalactose
[127]. Serine-bound keratan sulphate and chondroitin sulphate chains in cartilage sit on the same
large, hyaluronic acid-linked core protein
(Fig. 13.14). The presence of keratan sulphate in
various invertebrates has been claimed but only
on the basis of subunit analysis of the mucopolysaccharides and not on detailed structural analyses [123].
The approximately 1-MDa unbranched hyaluronic acids are found in vertebrates in, for example, connective tissue, the synovial fluids of joints
and the vitreous humour of the eye. They occupy a
central position in the macromolecular complexes
of the cartilage matrix (Fig. 13.14) and have considerable water-binding capacity. Surprisingly, corresponding polysaccharides have been detected in
bacteria. Amongst the invertebrates, the probable
presence of hyaluronic acid has been shown in
many species by histochemical methods but it has
been isolated and chemically identified only in the
insects, e.g. in the peritrophic membrane of the
silkworm Bombyx mori, the midgut of the wax
moth Galleria melonella, and the nervous system
of the cockroach Periplaneta americana [123].
13.4.2 Glycan Sulphates
and Glycan Phosphates
The radula (odontrophore) on the underside of
the rasping tongue of the prosobranch snail Busycon canaliculatum has the macroscopic and histological character of a typical cartilage, but
has glucan sulphate instead of glycosaminoglycans. Hydrolysis of the glucan sulphate gives glu-
13 The Structure and Metabolism of Carbohydrates
their protein bonds. These polysaccharides are
also highly modified after their biosynthesis; the
resulting variability of the heparins is even
greater than that of the other glycosaminoglycans. The different heparin variants vary greatly
in their clotting-inhibitory activity in proportion
to the content of an oligosaccharide sequence
necessary for antithrombin binding [118].
A typical heparin has 70-90 % iduronic acid;
most glucosamine residues are N-sulphated and
only a few carry N-acetyl groups. The C-6, and
often the C-3, of the glucosamine is O-sulphated,
as is sometimes the C-2 of many of the iduronic
acids, but never glucuronic acid. Most of the
heparins have a molecular mass of 5-15 kDa;
individual chains carry galactose, xylose and
serine as components of a protein bond. Thus,
heparin is apparently synthesized as a proteoglycan and only later separated from the protein. A
"macromolecular" heparin of 1 MDa, isolated
from rat skin, has several polysaccharide chains
of 60-100 kDa and these sit on a protein component of very unusual amino acid composition: this
consists only of serine, glycosylserine and glycine
and is protease resistant. Heparan sulphate
appears to be a somewhat modified form of heparin but it is probably more correctly looked upon
as an independent family of the glycosaminoglycans [89]; it has no clotting-inhibitory activity.
Only a few glucosamine residues are deacetylated
and can thus be N-sulphated; because of the
specificity of the corresponding enzyme, this
lower N-sulphation leads to a reduction in the
epimerization of glucuronic acid to iduronic acid
[273].
Heparin is thought to be absent from the lower
vertebrates; it has been sought without success in
the lamprey Petromyzon marinus, the shark
Squalus acanthias and the teleosts Sebastes marinus and Cyprinus carpio [120]. As the quantity of
clotting-active heparins is relatively low in mammalian organs, a practical source for this substance was sought amongst the invertebrates. In
fact, the mussels Spisula solidissima, Cypridina
islandica, Anomalocardia brasiliana and Tivela
mactroides contain considerable amounts of
heparin-like polysaccharides which have a large
proportion of antithrombin-binding sequences
and a corresponding clotting-inhibitory activity.
The glycosaminoglycan from C. islandica is
known as mactin [210]. An unusual heparin sulphate with many sulphate groups, little iduronic acid
and low clotting-inhibitory activity has been isolated from the lobster; most of the disaccharides
in this case consist of glucuronic acid and
glucosamine-N,O-bissulphate, whilst the nonsulphated or mono-sulphated units of the typical
vertebrate heparan sulphate are rare [120].
In vertebrates, there are two types of proteoglycan with the repetitive sequence of keratan
sulphate (Fig. 13.13). Type I from the cornea has
a molecular mass of about 80 kDa and contains
one to three polysaccharide chains bound
N-glycosidically to asparagine via N-acetylglucosamine. Such a bond has also been found
in a keratan sulphate from the skin of the teleost
Scomber japonicus. This type of carbohydrateprotein bonding is typical of glycoproteins which
arise by the transfer of a dolichol-bound oligosaccharide to an asparagine residue. Type-II keratan
sulphate is present in various connective tissues
and is bound O-glycosidically via N-acetylgalactosamine to serine or threonine. The binding
N-acetylgalactosamine residue is commonly substituted by N-acetylglucosamine or sialylgalactose
[127]. Serine-bound keratan sulphate and chondroitin sulphate chains in cartilage sit on the same
large, hyaluronic acid-linked core protein
(Fig. 13.14). The presence of keratan sulphate in
various invertebrates has been claimed but only
on the basis of subunit analysis of the mucopolysaccharides and not on detailed structural analyses [123].
The approximately 1-MDa unbranched hyaluronic acids are found in vertebrates in, for example, connective tissue, the synovial fluids of joints
and the vitreous humour of the eye. They occupy a
central position in the macromolecular complexes
of the cartilage matrix (Fig. 13.14) and have considerable water-binding capacity. Surprisingly, corresponding polysaccharides have been detected in
bacteria. Amongst the invertebrates, the probable
presence of hyaluronic acid has been shown in
many species by histochemical methods but it has
been isolated and chemically identified only in the
insects, e.g. in the peritrophic membrane of the
silkworm Bombyx mori, the midgut of the wax
moth Galleria melonella, and the nervous system
of the cockroach Periplaneta americana [123].
13.4.2 Glycan Sulphates
and Glycan Phosphates
The radula (odontrophore) on the underside of
the rasping tongue of the prosobranch snail Busycon canaliculatum has the macroscopic and histological character of a typical cartilage, but
has glucan sulphate instead of glycosaminoglycans. Hydrolysis of the glucan sulphate gives glu-