Uitto J, Lichtenstein J R
J Invest Dermatol. 1976 Feb;66(02):59-79. doi: 10.1111/1523-1747.ep12481404.
The collagens are the major structural glycoproteins of connective tissues. A unique primary structure and a multiplicity of post-translational modification reactions are required for normal fibrillogenesis. The post-translational modifications include hydroxylation of prolyl and lysyl residues, glycosylation, folding of the molecule into triple-helical conformation, proteolytic conversion of precursor procollagen to collagen, and oxidative deamination of certain lysyl and hydroxylysyl residues. Any defect in the normal mechanisms responsible for the synthesis and secretion of collagen molecules or the deposition of these molecules into extracellular fibers could result in abnormal fibrillogenesis; such defects could result in a connective tissue disease. Recently, defects in the regulation of the types of collagen synthesized and in the enzymes involved in the post-translational modifications have been found in heritable diseases of connective tissue. Thus far, the primary heritable disorders of collagen metabolism in man include lysyl hydroxylase deficiency in Ehlers-Danlos syndrome type VI, p-collagen peptidase deficency in Ehlers-Danlos syndrome type VII, decreased synthesis of type III collagen in Ehlers-Danlos syndrome type IV, lysyl oxidase deficency in S-linked cutis laxa and Ehlers-Danlos syndrome type V, and decreased synthesis of type I collagen in osteogenesis imperfecta.
胶原蛋白是结缔组织的主要结构糖蛋白。正常的纤维形成需要独特的一级结构和多种翻译后修饰反应。翻译后修饰包括脯氨酰和赖氨酰残基的羟基化、糖基化、分子折叠成三螺旋构象、前体原胶原蛋白向胶原蛋白的蛋白水解转化以及某些赖氨酰和羟赖氨酰残基的氧化脱氨。负责胶原蛋白分子合成和分泌或这些分子沉积到细胞外纤维中的正常机制中的任何缺陷都可能导致异常的纤维形成；此类缺陷可能导致结缔组织疾病。最近，在结缔组织遗传性疾病中发现了合成的胶原蛋白类型调节以及参与翻译后修饰的酶方面的缺陷。迄今为止，人类胶原蛋白代谢的主要遗传性疾病包括VI型埃勒斯-当洛综合征中的赖氨酰羟化酶缺乏、VII型埃勒斯-当洛综合征中的Ⅲ型胶原蛋白肽酶缺乏、IV型埃勒斯-当洛综合征中III型胶原蛋白合成减少、X连锁皮肤松弛症和V型埃勒斯-当洛综合征中的赖氨酰氧化酶缺乏，以及成骨不全中I型胶原蛋白合成减少。
