Glycosphingolipids (GSLs) are amphiphilic constituents of the outer leaflet of eukaryotic plasma membranes. In vivo degradation of GSLs takes place predominantly in the lysosome by the stepwise release of monosaccharide units from the nonreducing end of the oligosaccharide chain via specific exohydrolases (Fig. 1). Several of these enzymes need assistance of small glycoprotein cofactors, the so-called ‘sphingolipid activator proteins’. These are low molecular weight glycoproteins, which by themselves are catalytically inactive but are required as cofactors to facilitate interactions between membrane-bound hydrophobic sphingolipids and water-soluble exohydrolases in the lysosome, either by direct activation of their respective enzymes or as biological detergents that lift substrates out of the membrane in which sphingolipids are embedded. Five sphingolipid activation proteins (GM2 activator protein, and four saposins) encoded by two distinct genes are known. One gene encodes the GM2-activator protein, the other encodes prosaposin, the precursor protein of four saposins (Sandhoff et al. 2001; Kolter and Sandhoff 2005). This review limits its scope primarily to the activator function of the sphingolipid activator proteins but these proteins have other functions, such as lipid-binding and lipid-transfer proteins.
KeywordsGauche Disease Roche Molecular Biochemical Metachromatic Leukodystrophy Purkinje Cell Degeneration Globoid Cell Leukodystrophy
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