Krane S M, Pinnell S R, Erbe R W
Proc Natl Acad Sci U S A. 1972 Oct;69(10):2899-903. doi: 10.1073/pnas.69.10.2899.
Cell culture studies were performed on members of a family in which two sisters, ages 9 and 12, have a similar disorder characterized clinically by severe scoliosis, joint laxity and recurrent dislocations, hyperextensible skin, and thin scars. The skin collagen from the sisters was markedly deficient in hydroxylysine, but other amino acids were present in normal amounts. Hydroxylysine in collagen from fascia and bone was reduced to a lesser extent. Since the most likely explanation for the hydroxylysine deficiency was a reduction in enzymatic hydroxylation of lysine residues in protocollagen, we measured the activity of lysyl-protocollagen hydroxylase in crude lysates of cultured skin fibroblasts. Enzyme activities in the two affected children were 14 and 10% of controls, whereas the activity was about 60% of normal in the mother, a pattern most consistent with autosomal recessive inheritance. The mutant enzyme demonstrated the same cofactor requirements as that from normal cells. Deficiency of lysyl-protocollagen hydroxylase is the first inborn error of human collagen metabolism to be defined at the biochemical level.
对一个家族的成员进行了细胞培养研究，该家族中有两名姐妹，年龄分别为9岁和12岁，患有类似疾病，临床特征为严重脊柱侧弯、关节松弛和反复脱位、皮肤过度伸展以及瘢痕较薄。姐妹俩的皮肤胶原蛋白中羟赖氨酸明显缺乏，但其他氨基酸含量正常。筋膜和骨骼胶原蛋白中的羟赖氨酸减少程度较小。由于羟赖氨酸缺乏最可能的解释是原胶原蛋白中赖氨酸残基的酶促羟化作用降低，我们测量了培养的皮肤成纤维细胞粗裂解物中赖氨酰 - 原胶原蛋白羟化酶的活性。两名患病儿童的酶活性分别为对照的14%和10%，而母亲的活性约为正常的60%，这种模式最符合常染色体隐性遗传。突变酶表现出与正常细胞的酶相同的辅因子需求。赖氨酰 - 原胶原蛋白羟化酶缺乏是在生化水平上确定的人类胶原蛋白代谢的首个先天性缺陷。
