Brain glucocerebrosidase in Gaucher's disease
L. B. Daniels, P. J. Coyle, R. H. Glew, N. S. Radin and R. S. Labow
Using glucocerebroside labeled with carbon 14 as the substrate, we
determined that homogenates of brain tissue from both neuropathic and
nonneuropathic cases of Gaucher's disease were profoundly deficient (more
than 85%) in glucocerebrosidase activity. The beta-glucosidase activity, as
measured with 4-methylumbelliferyl-beta-D-glucopyranoside as the substrate,
in the homogenates of brain from four cases of Gaucher's disease was less
sensitive to inhibition by conduritol B epoxide (CBE) when compared with
normal brain beta-glucosidase. However, when homogenates were assayed with
radiolabeled glucocerebroside as the substrate, no differential sensitivity
toward CBE was indicated, suggesting the presence of an additional,
CBE-insensitive, beta-glucosidase in brain tissue. Residual
glucocerebrosidase activity partially purified from the brain of an adult
with type 1 Gaucher's disease was activated threefold by gluconoyl
hydrazine, whereas the same enzyme from control brain was unaffected, and
eight times less sensitive to gluconolactone inhibition.
