Hoogeveen A T, Graham-Kawashima H, d'Azzo A, Galjaard H
J Biol Chem. 1984 Feb 10;259(3):1974-7.
The nature of the molecular defect resulting in the beta-galactosidase deficiency in different forms of GM1-gangliosidosis and mucopolysaccharidosis IV B (Morquio B syndrome) was investigated. Normal and mutant cultured skin fibroblasts were labeled in vivo with [3H]leucine and immunoprecipitation studies with human anti-beta-galactosidase antiserum were performed, followed by polyacrylamide gel electrophoresis and fluorography. In Morquio B syndrome, the mutation does not interfere with the normal processing and intralysosomal aggregation of beta-galactosidase. In cells from infantile and adult GM1-gangliosidosis, 85-kDa precursor beta-galactosidase was found to be synthesized normally but more than 90% of the enzyme was subsequently degraded at one of the early steps in posttranslational processing. The residual 5-10% beta-galactosidase activity in adult GM1-gangliosidosis is 64-kDa mature lysosomal enzyme with normal catalytic properties but with a reduced ability of the monomeric form to aggregate into high molecular weight multimers. Knowledge of the exact nature of the molecular defect underlying beta-galactosidase deficiency in man may lead to a better understanding of the clinical and pathological heterogeneity among patients with different types of GM1-gangliosidosis and Morquio B syndrome.
研究了导致不同形式的GM1神经节苷脂贮积症和黏多糖贮积症IV B型（莫尔基奥B综合征）中β-半乳糖苷酶缺乏的分子缺陷的性质。用[3H]亮氨酸在体内标记正常和突变的培养皮肤成纤维细胞，并用人类抗β-半乳糖苷酶抗血清进行免疫沉淀研究，随后进行聚丙烯酰胺凝胶电泳和荧光自显影。在莫尔基奥B综合征中，突变并不干扰β-半乳糖苷酶的正常加工和溶酶体内聚集。在婴儿型和成人型GM1神经节苷脂贮积症的细胞中，发现85 kDa的β-半乳糖苷酶前体正常合成，但超过90%的酶在翻译后加工的早期步骤之一随后被降解。成人GM1神经节苷脂贮积症中残留的5-10%的β-半乳糖苷酶活性是64 kDa的成熟溶酶体酶，具有正常的催化特性，但单体形式聚合成高分子量多聚体的能力降低。了解人类β-半乳糖苷酶缺乏背后分子缺陷的确切性质，可能有助于更好地理解不同类型GM1神经节苷脂贮积症和莫尔基奥B综合征患者的临床和病理异质性。
