Mannosidosis: Separation and characterization of two acid α-mannosidase forms in mutant fibroblasts

Two acidic forms of α-mannosidase activity, A and B, are separated and characterized in fibroblasts from controls and patients with mannosidosis. In normal cells, A and B differ in adsorption on DEAE-cellulose, electrophoretic mobility, stability at 70°C and resistance to freezing at -20°C. In 5 of 6 mutant cell lines, A and B both exhibit altered Km's for artificial substrates and decreased thermal stability. Zn²⁺ has no effect on A or B in mutant or normal cells. In contrast, Co²⁺ slightly inhibits B in normal cells but markedly enhances the activity of B in mutant cells. The mutation in mannosidosis clearly results in an alteration in the biochemical characteristics of both major acidic forms of α-mannosidase.