The occurrence of two immunologically distinguishable beta-glucocerebrosidases in human spleen

Abstract

The β-glucosidase activity in spleen from control subjects and patients with different clinical phenotypes of Gaucher's disease was characterized. The occurrence of a soluble non-specific β-glucosidase with a neutral pH optimum and two membrane-associated β-glucocerebrosidases with an acid pH optimum was demonstrated. The two β-glucocerebrosidases can be distinguished on the basis of their ability to react with anti-(placental β-glucocerebrosidase) antibodies bound to protein-A – Sepharose 4B beads. One of the splenic β-glucocerebrosidases (form I) is precipitated by the immobilized antibodies and the other (form II) is not. The two forms also differ in binding affinity to concanavalin A, degree of stimulation of enzymic activity by taurocholate and isoelectric point. In contrast, the K_m values of the two β-glucocerebrosidases for natural and artificial substrates are similar and both are inhibited by conduritol B-epoxide. In spleen from three patients with type 1, one patient with type 2 and one patient with type 3 Gaucher's disease form I β-glucocerebrosidase was found to be clearly deficient, whereas the activity of form II was 25–50% of that in control spleen. The non-specific, neutral β-glucosidase was not deficient in these Gaucher spleens. The distinct biochemical and immunological properties of non-specific β-glucosidase and the fact that normal levels of the enzyme are present in patients with Gaucher's disease indicate, in confirmation of previous reports, that non-specific β-glucosidase is not related to β-glucocerebrosidase.