Human brain cerebroside beta-galactosidase: deficiency of transgalactosidic activity in Krabbe's disease.
Under experimental conditions optimal for the assay of D-galactosyl-N-acylsphingosine galactohydrolase (EC 3.2.1.46) activity, homogenates of neurologically normal human brain tissue could transfer galactose from galactosyl ceramide (gal-cer), lactosyl ceramide (lac-cer), 4-methylumbelliferyl-beta-galactoside (4-MU-gal), or p-nitrophenyl-beta-galactoside (PNP-gal) to [1-14C]oleoyl sphingosine, but homogenates of brain tissue from patients with Krabbe's disease lacked this ability. The rate of hydrolysis of ganglioside GM1 and, to a lesser extent, of PNP-gal by homogenates of Krabbe's brain tissue was also decreased. Activity of PNP-beta-galactosidase in normal brain tissue, like that of cerebroside beta-galactosidase from the same source, was considerably more heat-stable than the activity of either 4-MU-beta-galactosidase or the predominant GM1 beta-D-galactosidase (EC 3.2.1.23). Lac-cer and GM1, as well as 4-MU-gal and PNP-gal, were competitive inhibitors of human-brain cerebroside beta-galactosidase. These findings confirm the ability of mammalian cerebroside beta-galactosidase to catalyze a transgalactosylation reaction and provide additional information on the substrate specificity of human brain cerebroside beta-galactosidase.
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000201:enzymology*; D002675:Child, Preschool; D005260:Female; D005696:Galactosidases / Q000378:metabolism*; D005698:Galactosylceramidase / Q000378:metabolism*; D005776:Gaucher Disease / Q000201:enzymology; D006596:Hexosaminidases / Q000032:analysis; D006801:Humans; D007223:Infant; D007700:Kinetics; D007965:Leukodystrophy, Globoid Cell / Q000201:enzymology*; D007966:Leukodystrophy, Metachromatic / Q000201:enzymology; D008297:Male; D013379:Substrate Specificity; D013661:Tay-Sachs Disease / Q000201:enzymology; D001616:beta-Galactosidase / Q000378:metabolism; D001617:beta-Glucosidase / Q000378:metabolism
D005696:Galactosidases; D006596:Hexosaminidases; D001617:beta-Glucosidase; D001616:beta-Galactosidase; D005698:Galactosylceramidase