Comparison of the Acidic Lipid Requirement of Control and Type 1 Gaucher’s Disease Liver and Brain Glucocerebrosidases

Abstract

All patients with Gaucher’s disease, regardless of whether they have the non-neuronopathic form (type 1) or one of the neuronopathic forms (types 2 and 3), are profoundly deficient in lysosomal glucocerebrosidase activity. That the activity of glucocerebrosidase from normal spleen, liver, and brain has a near absolute lipid requirement is conveniently demonstrated by extracting the enzyme preparation sequentially with a bile salt (e.g., sodium cholate) and ice-cold n-butanol (1). This process, by delipidating the enzyme, renders glucocerebrosidase inactive. The inactive enzyme from spleen of controls and patients with type 1 Gaucher’s disease can be extensively reconstituted with exogenous acidic lipids (e.g., phosphatidylserine, galactocerebroside-3-sulfate, GM1) or the bile salt sodium taurodeoxycholate (2,3). The mutant glucocerebrosidase of the more severely affected type 2 patients, either before or after sodium cholate extraction and n-butanol delipidation, cannot be activated by the inclusion of bile salts or any of the above-mentioned acidic natural membrane lipids in the assay medium.

This investigation was supported by a grant (GM31319) from the United States Public Health Service, National Institutes of Health.