Ganglioside GM1 metabolism in living human fibroblasts with beta-galactosidase deficiency.

Abstract

The uptake and catabolism of [3H-ceramide]-GM1 was followed in living fibroblasts from patient with different forms of beta-galactosidase deficiency. Gangliosides are identified according to the nomenclature of Svennerholm (1963). A total inability to metabolize the ingested substrate was found in infantile GM1-gangliosidosis whereas cells from an adult GM1-gangliosidosis variant showed a slower rate of degradation, compared with controls. Morquio B fibroblasts had a comparable catabolism of GM1 as controls. Fibroblasts from different types of galactosialidosis, a recessive disease associated with a coexistent beta-galactosidase/neuraminidase deficiency all showed degradation of ingested GM1. In view of the molecular defect in this disease, this catabolism must be due to the 10-20% of monomeric beta-galactosidase molecules present in the lysosomes. Unexpectedly, in these cells an impaired metabolism of GM3 was found. The same finding was observed when cells with an isolated neuraminidase deficiency (mucolipidosis I) were loaded with GM1. A hypothesis is presented to explain these results.