Abstract
The biosynthesis of the acid mucopolysaccharides, hyaluronic acid and chondroitin sulfuric acid, occurs by way of uridine nucleotides which contain the monosaccharide units of the respective polysaccharides. The mechanism of alternation of groups is as yet unknown. Certain of the acid mucopolysaccharides are covalently bound to protein by way of serine. In the case of the protein-polysaccharide complex of cartilage, there is evidence to suggest that the polysaccharide may be linked to the serine by way of galactose. Chondroitin sulfuric acid B may be isolated almost free of amino acids from the tissues and urine of patients with the Hurler syndrome without the use of proteolytic enzymes, acid, or alkali. This contrasts markedly with the tight binding of this compound to protein in normal tissue. It is suggested that the metabolic defect in this disease may reside in a defect of the peptide or linkage of the peptide to polysaccharide resulting in failure of the acid mucopolysaccharide to be fixed normally in connective tissue. Such a defect may result in interference with normal regulation of polysaccharide synthesis with a resultant increased synthesis. It is proposed that such a mechanism may obtain in other heritable connective tissue diseases as well as other storage diseases.