Dermatan sulfate biosynthesis

With dermatan sulfate, biosynthesis of the L-iduronic acid residue poses another problem. Incorporation of D-glucose-6-C into rat skin indicated that L-iduronic acid is derived from D-glucose without scission of the carbon chain (R7). A sulfotransferase has been isolated from rabbit skin (D4) which is specific for sulfation of a chemically desul-fated dermatan sulfate. However, the degree of sulfation achieved by this enzyme amounted to only one sulfate group per five or six disaccharide units. 

The HS C5-epimerase that catalyzes the conversion of GlcA to IdoA has been cloned from bovine lung [41]. This enzyme is distinct from the epimerase involved in dermatan sulfate biosynthesis [42]. IdoA has a more flexible conformation than GlcA [43], and the formation of IdoA in GAGs is therefore believed to generally promote binding of the polysaccharides to proteins. The GlcA C5-epimerization is the only modification reaction in heparin/HS biosynthesis that cannot be reproduced without an enzyme catalyst [44]. 

K. Schwarz, B. Breuer, and H.Kresse, Biosynthesis and properties of a further member of the small chondroitin/dermatan sulfate proteoglycan family. J. Biol. Chem., 256 (1990) 22,023-22,028. 

Silbert JE, Sugumaran G. Biosynthesis of chondrotin/dermatan sulfate. lUBMB Life 2002 54 177-186. 

Malmstrom A, Aberg L. Biosynthesis of dermatan sulfate -assay and properties of the uronosyl C-5 epimerase. Biochem. J. 1982 201(3) 489-493. 

Malmstrom A, Fransson LA. Biosynthesis of dermatan sulfate. I. Formation of L-iduronic acid residues. J Biol Chem 1975 250 3419-3425. 

Quentin E, Gladen A, Roden L, Kresse H. A genetic defect in the biosynthesis of dermatan sulfate proteoglycan galactosyltransferase I deficiency in fibroblasts from a patient with a progeroid syndrome. Proc Natl Acad Sci U S A 1990 87 1342-1346. 

Examples of the use of induced biosynthetic effects for the deduction of the processes involved include the use of puromycin and cyclohexi-mide. These compounds, according to experiments with other systems, inhibit protein synthesis. Thus the inhibition of biosynthesis of hyaluronic acid and dermatan sulfate in human fibroblast cultures (M13, M16), of hyaluronic acid in synovial cells (S31), and of chondroitin sulfate (HI) led to the conclusion that the synthesis of protein acceptor is necessary for the polysaccharide chain initiation. Comparison of the effects of 1-butanol on the biosynthesis of chick cartilage chondroitin sulfate and streptococcal hyaluronic acid led to the suggestion that binding of Mg + ions and the uridine diphosphate moiety results in stabilization of the spatial arrangement of the specific enzymes (S47, T4). 

Silbert, J. E., Sugumaran, G. (2002). Biosynthesis of chondroitin/dermatan sulfate. lUBMB Life, 54(4), 177-186. 

Whereas the problem of the biosynthesis of the carbohydrate skeleton of dermatan sulfate is still entirely in the realm of speculation, some concrete information exists concerning the sulfation of this polysaccharide. Despite the fact that the sulfate group is located in the C-4 position of the galactosamine residue in both dermatan sulfate and chondroitin 4-aulfate, different suifotransferases seem to be responsible for the sulfar tion of these compounds. Davidson and Riley (1960) purified partially a sulfotransferase from extracts of rabbit skin which exhibited acceptor specificity for dermatan (desulfated dermatan sulfate). On a quantitative... 

A number of other problems pertaining to the biosynthesis of dermatan sulfate could be mentioned, but since this entire area is still a matter of speculation rather than actual knowledge, only one additional question will be pointed out. It has been indicated by preliminary experiments that at least the immediate sequence of amino acids surrounding the carbohydrate-protein linkage in dermatan sulfate from skin is different from that found in the chondroitiii sulfate-protein of bovine nasal cartilage (Stern and Rod6n, 1969). It wall therefore be of interest to study the acceptor specificity of the xylose transfer reaction, since tw o different xylcffiyltransferases could conceivably be involved in the formation of dermatan sulfate and chondroitin sulfate. 

The biosynthesis of heparin and heparan sulfate presents a number of problems whicii are specific for these polysaccharides, including (1) the formation of a-g ycosidic linkages ratlier than 3-linkages which predominate among the other glycosaminog yeans (with the exception of the somewhat special ease of the cr-Iinked L-iduronic acid residues in dermatan sulfate) (2) the mechanism of sulfation of the amino groups and (3) the introduction of sulfate into the uronic acid residues. 

Biosynthesis of Chondroitin Sulfate and Dermatan Sulfate Proteoglycans... 

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