Glycosaminoglycans, 1-5, 9, 46-76,

The repeating disaccharide unit of the main chain of chondroitin sulfate is 50, with O-sulfo groups on the 4- or 6-hydroxyl groups of most 2-acetamido-2-deoxy-D-galactosyl residues. Fractions can be prepared 

Evidence for the structure of the main repeating-chain of chondroitin sulfate, as well as the sequence at the linkage region to protein, has come 

In sulfation, substitution of polymeric chondroitin and chondroitin sulfates A and C by a hen-oviduct preparation has been described. The sulfate donor is adenylyl sulfate 3 -phosphate and a non-sulfated 2-acetamido-2-deoxy-D-galactosyl residue positioned internally in the polymer chain can be substituted.230 Evidence has been presented for another activity (from quail oviduct) that sulfates carbon atom 6 of a 2-acetamido-2-deoxy-D-galactosyl 4-C-sulfate group at the nonreducing end of the chain, giving the 4,6-di-C-sulfate.231 

Biosynthetic studies on the formation of hyaluronic acid have yielded less information than have similar studies about the structure of chondroitin. Addition to small, well defined oligosaccharides has not been found. Using labelled nucleoside 5 -glycosyl diphosphates in a bacterial system, evidence has been obtained for the synthesis of hyaluronic acid of high molecular 

This structure resembles that of chondroitin sulfate, except that some of the /3-D-glucosyluronic residues of the repeating disaccharide unit are replaced by a-L-idosyluronic residues. The proportion of D-glucosyluronic residues in the polymer varies according to the source, but there can be more L-idosyluronic than D-glucosyluronic residues. 

Proteoglycan Core protein mol vt Type of GAG chains No. of chains Location Functions 

Aggrecan 210,000 Chondroitin and keratan sulfate -130 Cartilage Mechanical support large aggregates with hyaluronan 

Betaglycan 36,000 Chondroitin or dermatan sulfate 1 Cell surface and matrix Binds TGF-beta 

Perlecan 600,000 Heparan sulfate 2-15 Basal laminae Structural and filtering function in basal lamina 

This glycosaminoglycan consists of a linear chain of the repeating disaccharide units of [- 4)-P-D-glucopyranosyl uronic acid-(l— 3)-A -acetyl-2-amino-2-deoxy-p-D-glucopyranosyl-(l- ] (see Fig. 6.14A). It is composed of 500-50,000 monosaccharide residues per molecule [130]. 

Hyaluronic acid is widely distributed in mammalian cells and tissues. It is found in synovial fluid that lubricates the joints, in the vitreous humor of the eye, and in connective tissues such as the umbilical cord, the dermis, and the arterial wall. It also occurs as a capsular material around certain bacteria, usually pathogenic, such as Streptococci [130]. 

The chondroitin sulfates are major components of cartilage. Proteochron-droitin sulfates are found in the cornea of the eye, the aorta, skin, and lung tissue, where they are located between fibrous protein molecules and provide a soft, pliable texture. Hyaluronic acid and chondroitin sulfate represent heteropolysaccharides with two monosaccharides units with heterolinkages of (3-1 — 3 and p-1 4. 

Dermatan sulfate may be derived from chrondroitin-4-sulfate by the action of a C-5 epimerase that inverts the carboxylate group of the D-glucuronic acid residue. 

This forms a repeating disaccharide of [ 4)-a-L-idopyranosyl uronic acid-(1 - 3)-P-D-A-acetyl-2-amino-2-deoxy-4-sulfato- 3-D-galactopyranosyl-(l ]. The epimerization reaction is usually incomplete so that there are also some d-glucuronic acid residues (see Fig. 6.14C) [131]. 

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Glycosaminoglycans Glycose Glyco Serve Glycosidases Glycoside Glycosides... 

There are other glycosaminoglycans. Hyaluronic acid [9004-61-9] occurs both free and in noncovalent association with proteoglycan molecules. Heparin [9005-49-6] and heparan sulfate [39403-40-2] also known as heparitin sulfate [9050-30-0] occur in mast cells and in the aorta, Hver, and lungs. 

Compounds with similar stmctures, ie, polysaccharide chains covalentiy attached to polypeptide chains, but where the polysaccharides are not glycosaminoglycans, are found commonly in plants and are known as protein-polysaccharides. 

FIGURE 9.31 The known proteoglycans include a variety of structures. The carbohydrate groups of proteoglycans are predominantly glycosaminoglycans O-linked to serine residues. Proteoglycans include both soluble proteins and integral transmembrane proteins. 

Proteoglycan Glycosaminoglycan Protein M, Number of Amino Acid Residues... 

FIGURE 9.32 Proteoglycans serve a variety of functions on the cytoplasmic and extracellular surfaces of the plasma membrane. Many of these functions appear to involve the binding of specific proteins to the glycosaminoglycan groups. 

Danaparoid (Orgaran mean MW, 6,000 Da) is a mixture of nonheparin glycosaminoglycans derived from pig gut (dermatan sulfate, heparan sulfate, chondroitin sulfate). Die anti-Xa/anti-IIa ratio (22 1) is even greater than seen with LMWH. Die anti-IIa effect may be mediated in part by dermatan sulfate, which catalyzes thrombin inhibition by heparin cofactor II. 

For polysaccharides containing a substantial proportion of amino sugar residues, the term polysaccharide is adequate, although the term glycosaminoglycan may be used where particular emphasis is desired. 

D-Xylose Wood gums, proteoglycans, glycosaminoglycans. Constituent of glycoproteins. ... 

Amino Sugars (Hexosamines) Are Components of Glycoproteins, Gangliosides, Glycosaminoglycans... 

Figure 13-14. Structure of some complex polysaccharides and glycosaminoglycans.

Lindahl U, Hook M Glycosaminoglycans and their binding to biological macromolecules. Annu RevBiochem 1978 47 385. 

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