BETA-GLUCOSIDASES IN GAUCHER DISEASE

高谢病，最常见的遗传性溶酶体脂储存 人类的疾病是由于葡萄糖脑苷酶的缺乏引起的： 葡萄糖脑苷酶导致葡萄糖脑苷在体内的积累 内脏组织、骨髓的巨噬细胞系统的细胞，以及 在某些情况下，是大脑。人体的生理功能及其可能 第二种β-葡萄糖苷酶a的病理生理学意义 广谱特异性胞浆酶，在人体组织中的作用尚不清楚。我们的 主要目的是研究其物理化学性质和动力学性质。 人肝葡萄糖脑苷酶和胞浆β-葡萄糖苷酶。我们会 确定这两种酶是否有任何共同的结构特征。动能 组织中残留的葡萄糖脑苷酶活性的性质 非神经性和神经性高谢病的病例将是 与正常组织比较。在这些比较中的一个关键工具 研究将是从高雪脾中提取的耐热糖蛋白 激活葡萄糖脑苷酶。的结构和功能 热稳定因素也将被调查。进一步加深我们对 这两个突出的物理化学性质和动力学性质 来自人体组织的β-葡萄糖苷酶可以提供对 导致高谢病的多种形式的生化基础。

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.