Galactosylceramide and galactosylsphingosine loading studies in cultured skin fibroblasts in human and murine globoid cell leukodystrophy.

Cell level studies of 3H-galactosylceramide(GalCer) and 3H-galactosyl sphingosine (GalSph) have been carried out in cultured skin fibroblasts from human and murine globoid cell leukodystrophy (GLD). GalCer loading studies disclosed that the hydrolysis rates of GalCer in human control and GLD were 72% and 45%, respectively, and those from the murine control and GLD cells were 77% and 21%, respectively, on the 5th day of culture. On the other hand, GalSph loading studies showed that the hydrolysis rate of GalSph in the human control and GLD were 40% and 10%, respectively, and those from murine control and GLD cells were 38% and 10% on the 12th day of culture. These data suggest that both GalCer and GalSph degradations were impaired in cell level in human and murine GLD. Furthermore, when radioactive 3H-GalSph was loaded into cultured fibroblasts from murine and human GLD, 3H-GalCer band was formed via GalSph. These data strongly suggest that GalCer could be synthesized through the GalSph route as a minor pathway at least in cultured skin fibroblasts, although the major pathway to synthesize GalCer should be via ceramide.