Correlation between Residual Activity of a Lysosomal Hydrolase and the Severity of the Resulting Storage Disease
Glycosphingolipids (GSL) are components of the outer leaflet, of animal plasma membranes. Sialoglycosphingolipids (ganglio-sides) are especially enriched in neuronal cell surfaces. Biosynthesis of GSL is catalyzed by enzymes bound to the membranes of the endoplasmic reticulum and the Golgi stacks whereas the final degradation of these amphophilic GSL takes place in secondary lysosomes. Electron spin resonance studie with nitroxide labelled gangliosides (Schwarzrnann et al. (1983); Schwarzmariri et al. (1984)) and metabolic studies (Sonderfeld et al. (1985) suggest that gangliosides added to the medium of cultured human fibroblasts insert into the plasma membrane from where they can be transported into the lysosomal compartment for sequential degradation by exo-hydrolases. In mutant cells, with a block in lysosomal GSL degradation, undegradable intermediates accumulate, for example ganglioside GM2 in Tay Sachs disease. Blocs in lysosomal GSL catabolism are caused by mutations either in GSL hydrolases or in GSL-binding proteins which stimulate th degradation of some membrane-bound GSL by lysosomal hydrolases (Sandhoff et al. (1989); Conzelmann and Sandhoff (1987); Fürst et al. (1988); Schröder et al. (1989); Nakario et al. (1989)).
KeywordsHydrolase Nitroxide Leukodystrophy Gangliosidosis
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