BETA-GLUCOSIDASES IN GAUCHER DISEASE

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Gaucher disease, the most common hereditary lysosomal lipid storage disorder in man, is caused by a deficiency of the enzyme glucocerebroside: glucocerebrosidase resulting in the accumulation of glucocerebroside in cells of the macrophage system of visceral tissue, bone marrow, and, in some cases, the brain. The physiologic function and possible pathophysiologic significance of a second beta-glucosidase, a broad-specificity cytosolic enzyme, in human tissues is not known. Our primary goal is to investigate the physical-chemical and kinetic properties of human liver glucocerebrosidase and cytosolic beta-glucosidase. We will determine if the two enzymes share any structural features. The kinetic properties of the residual glucocerebrosidase activity present in tissues of cases of non-neuronopathic and neuronopathic Gaucher disease will be compared with that of normal tissues. A key tool in these comparative studies will be the heat-stable glycoprotein from Gaucher spleen that activates glucocerebrosidase. The structure and function of the heat-stable factor will also be investigated. Furthering our knowledge of the physical-chemical and kinetic properties of these two prominent beta-glucosidases from human tissues could provide insight into the biochemical basis which accounts for the diverse forms of Gaucher disease.