DORFMAN A
Biophys J. 1964 Jan;4(1 Pt 2):SUPPL155-65. doi: 10.1016/s0006-3495(64)86935-6.
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.
酸性粘多糖、透明质酸和硫酸软骨素的生物合成是通过含有各自多糖单糖单位的尿苷核苷酸进行的。基团交替的机制尚不清楚。某些酸性粘多糖通过丝氨酸与蛋白质共价结合。就软骨的蛋白多糖复合物而言,有证据表明多糖可能通过半乳糖与丝氨酸相连。在不使用蛋白水解酶、酸或碱的情况下,可从患有胡尔勒综合征患者的组织和尿液中分离出几乎不含氨基酸的硫酸软骨素B。这与该化合物在正常组织中与蛋白质的紧密结合形成明显对比。有人认为,这种疾病的代谢缺陷可能在于肽的缺陷或肽与多糖的连接缺陷,导致酸性粘多糖无法正常固定在结缔组织中。这样的缺陷可能会干扰多糖合成的正常调节,从而导致合成增加。有人提出,这种机制可能也存在于其他遗传性结缔组织疾病以及其他贮积病中。