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The structure and metabolism of mucopolysaccharides (glycosaminoglycans) and the problem of the mucopolysaccharidoses

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      Abstract

      The structures of the sulfated mucopolysaccharides are outlined and their common and particular features pointed out. All are normally attached to specific proteins by covalent linkages to form large complex molecules.
      The biosynthesis of the sulfated mucopolysaccharides is considered in relation to the possible genetic defects of the mucopolysaccharidoses. The formation of the core protein is a prerequisite for the subsequent synthesis of the carbohydrate chains in both normal and abnormal cells. A linkage region consisting of atypical neutral sugars that joins the carbohydrate chain to protein is common to all the sulfated mucopolysaccharides apart from keratan sulfate. The formation of this region is strictly controlled by the specificities of the glycosyl transferases that form it. The synthesis of the main carbohydrate chain is dependent on prior formation of the linkage region so that a defect in the formation of the linkage region or in glycosylation of the core protein cannot explain the abnormalities of the mucopolysaccharide diseases.
      Other possible explanations are considered, including defects in protein-polysaccharide structures that might produce inbalance in synthesis and degradation. Faulty intracellular degradation of mucopolysaccharides has been shown in cultures of fibroblasts from patients with Hurler's and Hunter's syndromes, implying a deficiency of degradative enzymes. Deficiencies of certain lysosomal exo-glycosidases found in some tissues of patients with mucopolysaccharidoses is unlikely to be the primary defect in view of the specificities of these enzymes and the structures of the mucopolysaccharidoses.
      Some of the clinical features of the mucopolysaccharidoses may be explained by possible secondary effects of the accumulation of abnormal mucopolysaccharides within the body.
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