Proteoglycans: Biological Roles and Strategies
347
sulfated at C-6 is often associated with GleA-containing disaccharides (Karamanos et al. 1995b). Twenty three non- and variously sulfated disaccharides
have been so far identified (Karamanos et al. 1994). The molecular mass (Mr)
of GalAGs is often between 20 and 30-kDa, although higher MrS have been
determined in GalAGs isolated from invertebrates (Karamanos et al. 1992).
The GleAGs, heparin and HS, constitute another group of GAGs with a repeating
disaccharide structure distinctly different from other GAGs. The basic unit is
(~4 uronic acid~I~4GleNal~1. Therefore, the glycosidic linkage between
uronic acid and GleN is ~1~4 instead of ~1~3 and that between GleN and
uronic acid is al~4 instead of ~1~4. The uronic acid of the basic unit being DGleA or L-IdoA (Fig. 25.5). In this group of GAGs, hexosamine is not only Nacetylated but also N-sulfonylated. GleNSOr is generally less than 40-50 % of
total GleN in HS, whereas in heparin this structure accounts for more than
60-70 %. A minor portion of the amino group may also be underivatized. Any
free hydroxyl group may carry a sulfate, producing twelve non- and variously sulfated disaccharides (Karamanos et al. 1996, 1997). The frequent oversulfated unit
contains sulfate groups at C-2 of IdoA and at C-6 of glucosamine. Some other
infrequent sulfation patterns at C-3 of glucosamine and C-2 of GleA as a part of
longer sequences have important biological functions, such as the binding of
heparin to antithrombin-III (Lindahl 1989) and the regulation of heparin mitotic
activity (Syrokou et al. 1999). The molecular sizes of these GleAGs do not exceed
100-kDa and normally range from 15 to 30-kDa.
The repeating disaccharide structure of KS contains the same alternative
~1~3 and ~1~4 glycosidic bonds with those present in HA and GalAGs, but
with galactose in the position of the hexosamine and GleNAc in the position of
uronic acid (Fig. 24.3B). KS is also a sulfated GAG. Sulfate esters are generally
present at C-6 position of anyone of the monosaccharides. This GAG is synthesized on two different linkage oligosaccharide precursor, the structure of which
is dependent on the type of glycosidic linkage on the protein core. O-linked
linkage-region oligosaccharide is characteristic for mucins and N-linked for cellbound glycoproteins (Fig. 24.2). KS attached to the protein core via the O-linked
branched hexasaccharide is found in the large cartilage PG, the aggrecan. 0linked oligo saccharides of this type are also present in aggrecan and versican.
Sialic acids attached to this O-linked oligosaccharide regulate the synthesis of KS,
Le., KS elongation can occur by glycosyl-transferases and sulfotransferases only
when sialic acids are not present in the non-reducing terminal. After chain elongation, sialic acids are also added to the non-reducing end of the KS chain (Fig.
24.2). The mannose rich oligosaccharide is the precursor for the synthesis at the
biantennary N-linked oligosaccharide. The precursor is transferred to the asparagine residue which is a part of the peptide sequence Asn-xxx-Ser/Thr, in the
rough endoplasmic reticulum (Wight et al. 1991). Here also, when one or both of
the indicated sialic acids are not added (Fig. 24.2), the biantennary oligosaccharide can be elongated with KS chains. This type of N -linked KS is often in cartilage fibromodulin (KSPG) and cornea lumican (KSPG). The molecular mass of
KS is often lower than that of the other GAGs and seldom exceeds 5-kDa.
347
sulfated at C-6 is often associated with GleA-containing disaccharides (Karamanos et al. 1995b). Twenty three non- and variously sulfated disaccharides
have been so far identified (Karamanos et al. 1994). The molecular mass (Mr)
of GalAGs is often between 20 and 30-kDa, although higher MrS have been
determined in GalAGs isolated from invertebrates (Karamanos et al. 1992).
The GleAGs, heparin and HS, constitute another group of GAGs with a repeating
disaccharide structure distinctly different from other GAGs. The basic unit is
(~4 uronic acid~I~4GleNal~1. Therefore, the glycosidic linkage between
uronic acid and GleN is ~1~4 instead of ~1~3 and that between GleN and
uronic acid is al~4 instead of ~1~4. The uronic acid of the basic unit being DGleA or L-IdoA (Fig. 25.5). In this group of GAGs, hexosamine is not only Nacetylated but also N-sulfonylated. GleNSOr is generally less than 40-50 % of
total GleN in HS, whereas in heparin this structure accounts for more than
60-70 %. A minor portion of the amino group may also be underivatized. Any
free hydroxyl group may carry a sulfate, producing twelve non- and variously sulfated disaccharides (Karamanos et al. 1996, 1997). The frequent oversulfated unit
contains sulfate groups at C-2 of IdoA and at C-6 of glucosamine. Some other
infrequent sulfation patterns at C-3 of glucosamine and C-2 of GleA as a part of
longer sequences have important biological functions, such as the binding of
heparin to antithrombin-III (Lindahl 1989) and the regulation of heparin mitotic
activity (Syrokou et al. 1999). The molecular sizes of these GleAGs do not exceed
100-kDa and normally range from 15 to 30-kDa.
The repeating disaccharide structure of KS contains the same alternative
~1~3 and ~1~4 glycosidic bonds with those present in HA and GalAGs, but
with galactose in the position of the hexosamine and GleNAc in the position of
uronic acid (Fig. 24.3B). KS is also a sulfated GAG. Sulfate esters are generally
present at C-6 position of anyone of the monosaccharides. This GAG is synthesized on two different linkage oligosaccharide precursor, the structure of which
is dependent on the type of glycosidic linkage on the protein core. O-linked
linkage-region oligosaccharide is characteristic for mucins and N-linked for cellbound glycoproteins (Fig. 24.2). KS attached to the protein core via the O-linked
branched hexasaccharide is found in the large cartilage PG, the aggrecan. 0linked oligo saccharides of this type are also present in aggrecan and versican.
Sialic acids attached to this O-linked oligosaccharide regulate the synthesis of KS,
Le., KS elongation can occur by glycosyl-transferases and sulfotransferases only
when sialic acids are not present in the non-reducing terminal. After chain elongation, sialic acids are also added to the non-reducing end of the KS chain (Fig.
24.2). The mannose rich oligosaccharide is the precursor for the synthesis at the
biantennary N-linked oligosaccharide. The precursor is transferred to the asparagine residue which is a part of the peptide sequence Asn-xxx-Ser/Thr, in the
rough endoplasmic reticulum (Wight et al. 1991). Here also, when one or both of
the indicated sialic acids are not added (Fig. 24.2), the biantennary oligosaccharide can be elongated with KS chains. This type of N -linked KS is often in cartilage fibromodulin (KSPG) and cornea lumican (KSPG). The molecular mass of
KS is often lower than that of the other GAGs and seldom exceeds 5-kDa.