Incorporation and degradation of G M1 ganglioside and asialoG m1 ganglioside in cultured fibroblasts from normal individuals and patients with β-galactosidase deficiency

Abstract

The uptake and degradation of G M1 ganglioside (G M1) and asialoG M1 ganglioside (G A1) were studied in cultured fibroblasts from normal individuals and patients with β-galactosidase deficiency, using the lipid-loading test. The glycolipids were incorporated from the media into the fibroblasts and the terminal galactose was hydrolyzed in normal cells. The hydrolysis rates of G A1 were 80–86% of normal on the 3rd day after loading, while G M1 was hydrolyzed slowly; 35–54% on the 14th day. In infantile G M1 gangliosidosis and I-cell disease, little G M1 and G A1 was hydrolyzed on any day of culture, while fibroblasts from patients with adult G M1 gangliosidosis, Morquio disease type B and galactosialidosis hydrolyzed the lipids at nearly normal rates. The intracellular accumulation of the glycolipids, on the basis of protein content, was abnormally high in the case of infantile G M1 gangliosidosis and I-cell disease, but normal in the other disorders examined. These observations indicate that the in situ metabolism of G M1 and G A1 is probably normal in fibroblasts from patients with adult G M1 gangliosidosis, Morquio disease type B and galactosialidosis, although in vitro β-galactosidase activities in these disorders are very low. The results are compatible with findings that G M1 and G A1 do not accumulate in the somatic organs of patients with adult G M1 gangliosidosis and galactosialidosis. In I-cell disease, however, the results of the loading test did not agree with the finding that there is little accumulation of glycolipids in postmortem tissues.