Saposins (sap) A and C activate the degradation of galactosylsphingosine.
As previously shown for [(3)H-galactosyl]ceramide, the breakdown of [(3)H-galactosyl]sphingosine was reduced in prosaposin-deficient skin fibroblast homogenates. Galactosylsphingosine hydrolysis was also deficient in cell homogenates from Krabbe's disease (beta-galactocerebrosidase-deficient) patients, but not acid beta-galactosidase-deficient patients. Moreover, hydrolysis of galactosylsphingosine in the prosaposin-deficient cell homogenates could be partially restored by adding pure saposin A or C, thereby identifying these saposins as essential facilitators of galactosylsphingosine hydrolysis. By contrast, saposins B and D had little effect on galactosylsphingosine hydrolysis in the prosaposin-deficient cells. The reduced galactosylsphingosine turnover in prosaposin-deficiency suggests that there could be a pathogenetic cerebral accumulation of galactosylsphingosine in this disorder.
Harzer
K
K
Institut für Hirnforschung, Universität Tübingen, D-72070 Tübingen, Germany.
Hiraiwa
M
M
Paton
B C
BC
D000293:Adolescent; D000328:Adult; D002458:Cell Fractionation; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D005347:Fibroblasts / Q000378:metabolism; D005698:Galactosylceramidase / Q000172:deficiency / Q000378:metabolism; D005699:Galactosylceramides / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007965:Leukodystrophy, Globoid Cell / Q000201:enzymology* / Q000503:physiopathology; D009085:Mucopolysaccharidosis IV / Q000201:enzymology / Q000503:physiopathology; D011498:Protein Precursors / Q000378:metabolism; D011609:Psychosine / Q000378:metabolism*; D049231:Saposins; D012867:Skin / Q000166:cytology
D005699:Galactosylceramides; D006023:Glycoproteins; D011498:Protein Precursors; D049231:Saposins; D011609:Psychosine; D005698:Galactosylceramidase