Bovine brain
phosphatidylserine effectively activates human brain
galactosylceramidase (Hanada, E. and Suzuki, K. (1979) Biochim. Biophys. Acta 575, 410-420). Its effect on the other
beta-galactosidase (Gm1-ganglioside beta-galactosidase) in human tissues, genetically distinct from
galactosylceramidase, was examined. When partially purified human brain
beta-galactosidase preparations, pure with respect to each other, were used as the
enzyme source and when
lactosylceramide, a common
glycosphingolipid substrate for both
beta-galactosidases, was used as the substrate,
phosphatidylserine activated only hydrolysis of
lactosylceramide by
galactosylceramidase but not by GM1-ganglioside
beta-galactosidase. With either
galactosylceramide or
lactosylceramide as substrate, and with
phosphatidylserine as the activator, diagnosis of
globoid cell leukodystrophy was possible using whole homogenates of cultured fibroblasts. Since 80-90% of
lactosylceramide-cleaving activity in normal fibroblasts is due to GM1-ganglioside
beta-galactosidase and since fibroblasts of
globoid cell leukodystrophy patients are genetically deficient in
galactosylceramidase but normal in GM1-ganglioside
beta-galactosidase, these rsults are also consistent with specific activation of
galactosylceramidase by
phosphatidylserine.