Saposins (sap) A and C activate the degradation of galactosylsphingosine

As previously shown for [H-3-galactosyl]ceramide, the breakdown of [H-3-gal actosyl]sphingosine was reduced in prosaposin-deficient skin fibroblast hom ogenates. Galactosylsphingosine hydrolysis was also deficient in cell homog enates from Krabbe's disease (beta -galactocerebrosidase-deficient) patient s, but not acid beta -galactosidase-deficient patients. Moreover, hydrolysi s of galactosylsphingosine in the prosaposin-deficient cell homogenates cou ld be partially restored by adding pure saposin A or C, thereby identifying these saposins as essential facilitators of galactosylsphingosine hydrolys is. By contrast, saposins B and D had little effect on galactosylsphingosin e hydrolysis in the prosaposin-deficient cells. The reduced galactosylsphin gosine turnover in prosaposin-deficiency suggests that there could be a pat hogenetic cerebral accumulation of galactosylsphingosine in this disorder. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.