Comparison of rates of hydrolysis of N-oleoyl and N-stearoyl glucocerebroside in patients with Gaucher's disease.

The deficiency of oleic acid as one of the fatty acids in glucocerebrosides that accumulate (31--77 mg/g dry weight) in the spleen in patients with Gaucher's disease was confirmed in 9 cases. In an effort to account for the 10-fold difference between the oleoyl glycocerebroside content of glucocerebrosides in spleen from controls and patients with Gaucher's disease, we compared the ability of extracts of spleen and fibroblasts from individuals with various forms of Gaucher's disease and controls to hydrolyze [14C]stearoyl and [3H]oleoyl glucocerebroside. The residual glucosylceramidase activity in patients with Gaucher's disease hydrolyzes the glucose moiety of oleoyl glucocerebroside at approximately the same rate as that of stearoyl glucocerebroside. Similarly, the more active glucosylceramidase of control tissue acts upon both oleoyl and stearoyl glucocerebrosides with equal efficiency. These observations indicate that a mutation affecting the substrate specificity of glucosylceramidase cannot account for the lack of oleic acid-containing glucocerebrosides in patients with Gaucher's disease. Thus, the hypothesis that the difference in fatty acid composition found in glucocerebroside is obtained as a result of a mutation affecting the specificity of the residual glucosylceramidase must be rejected.