Metabolism and Structure-Function Relationships of Connective Tissue Glycosaminoglycans and Proteoglycans

Jeremiah   E.   Silbert

doi:10.2174/1385272043485864

Abstract

Connective tissue matrix contains the linear polysaccharide (glycosaminoglycan) hyaluronan, and the glycosaminoglycans chondroitin / dermatan sulfate, and keratan sulfate covalently linked to protein (proteoglycans). Hyaluronan is a linear polymer consisting of alternating N-acetylglucosamine and glucuronic acid residues; chondroitin / dermatan has alternating N-acetylgalactosamine and glucuronic or iduronic acid residues; keratan has galactose and N-acetylglucosamine residues. There are two classes of matrix proteoglycans named “hyalectin” and “SLRP (small leucine-rich protein).” Hyalectins have similar large core proteins and large numbers of glycosaminoglycan chains, while SLRPs have similar small core proteins with few glycosaminoglycan chains. Synthesis proceeds by modification of glucose to form specific sugar nucleotides that act as the direct precusors for forming the glycosaminoglycans and linkage oligosaccharides on specific amino acids of specific proteins. The chondroitin / dermatan and keratan are modified by variable sulfation and in the case of dermatan, by epimerization of some of the glucuronic to iduronic. These modifications provide for multiple structural variations that in turn provide a high degree of specificity in function. In general, the functions of matrix hyaluronan and the matrix proteoglycans relate to interactions with other matrix substances such as collagen to provide scaffolding and shape. Their variable structures provide specificity of function for particular tissues, and specific aspects of interaction with other matrix molecules.

Keywords: Proteoglycans, matrix, glycosaminoglycan, sulfation, keratan

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