Ginns E I, Brady R O, Pirruccello S, Moore C, Sorrell S, Furbish F S, Murray G J, Tager J, Barranger J A
Proc Natl Acad Sci U S A. 1982 Sep;79(18):5607-10. doi: 10.1073/pnas.79.18.5607.
Multiple molecular forms of beta-glucocerebrosidase that permit discrimination between neurologic and non-neurologic phenotypes of Gaucher disease have been identified radioimmunologically in fibroblasts and human brain tissue. In normal human fibroblasts these forms have been shown by NaDodSO4/polyacrylamide gel electrophoresis to have apparent Mr of 63,000 (form A1), 61,000 (form A2), and 56,000 (form B). The Mr 63,000 form may be a precursor of the Mr 56,000 form. Non-neurologic Gaucher disease (type 1) fibroblasts and normal brain tissue are characteristic in that they contain only one major immunoreactive protein, the Mr 56,000 form. In contrast, fibroblast extracts and brain tissue from neurologic Gaucher disease phenotypes contain only the higher molecular weight forms A1 and A2. These data and the low residual activity of the enzyme in all the variants of Gaucher disease suggest that the mutations of beta-glucocerebrosidase are allelic and involve the active site.
通过放射免疫法已在成纤维细胞和人脑组织中鉴定出多种β-葡萄糖脑苷脂酶分子形式，这些形式可用于区分戈谢病的神经型和非神经型表型。在正常人成纤维细胞中，通过十二烷基硫酸钠/聚丙烯酰胺凝胶电泳显示，这些形式的表观分子量分别为63,000（A1型）、61,000（A2型）和56,000（B型）。分子量63,000的形式可能是分子量56,000形式的前体。非神经型戈谢病（1型）成纤维细胞和正常脑组织的特征在于它们仅含有一种主要的免疫反应性蛋白，即分子量56,000的形式。相比之下，神经型戈谢病表型的成纤维细胞提取物和脑组织仅含有分子量较高的A1和A2形式。这些数据以及戈谢病所有变体中该酶的低残留活性表明，β-葡萄糖脑苷脂酶的突变是等位基因的，并且涉及活性位点。
