Furbish F S, Steer C J, Krett N L, Barranger J A
Biochim Biophys Acta. 1981 Apr 3;673(4):425-34. doi: 10.1016/0304-4165(81)90474-8.
The clearance of native human placental glucocerebrosidase by rat liver shows the presence of two distinct enzyme forms with different recognition characteristics. The clearance and uptake of native enzyme by liver cells was compared to that of glucocerebrosidase sequentially treated with neuraminidase, beta-galactosidase and beta-N-acetylglucosaminidase. The initial rate of clearance of infused enzyme was increased greater than 10-fold for the asialo-, agalacto- and ahexoenzymes over that of native glucocerebrosidase. Incorporation of asialo enzyme was increased in hepatocytes over that of native enzyme, while the distribution of agalacto- and ahexoenzyme preparations was increased in non-parenchymal cells. This observation is consistent with the identification of a galactose receptor on hepatocytes and N-acetylglucosamine/mannose receptors on Kupffer cells. These data and inhibition studies by specified monosaccharide-terminal glycoprotein derivatives demonstrate the importance of these sugars in the uptake of this lysosomal enzyme by receptor-mediated endocytosis. Modification of the enzyme to expose certain monosaccharide moieties results in increased delivery to specific cell types. Therefore, naturally occurring receptors can be utilized for targeting glucocerebrosidase to the non-parenchymal cell in liver.
大鼠肝脏对天然人胎盘葡萄糖脑苷脂酶的清除显示存在两种具有不同识别特征的不同酶形式。将肝细胞对天然酶的清除和摄取与依次用神经氨酸酶、β-半乳糖苷酶和β-N-乙酰葡糖胺酶处理的葡萄糖脑苷脂酶的清除和摄取进行了比较。去唾液酸酶、去半乳糖酶和去己糖酶注入酶的初始清除率比天然葡萄糖脑苷脂酶提高了10倍以上。肝细胞中去唾液酸酶的掺入比天然酶增加，而去半乳糖酶和去己糖酶制剂在非实质细胞中的分布增加。这一观察结果与肝细胞上半乳糖受体和枯否细胞上N-乙酰葡糖胺/甘露糖受体的鉴定一致。这些数据以及特定单糖末端糖蛋白衍生物的抑制研究证明了这些糖在受体介导的内吞作用中对这种溶酶体酶摄取的重要性。对酶进行修饰以暴露某些单糖部分会导致向特定细胞类型的递送增加。因此，天然存在的受体可用于将葡萄糖脑苷脂酶靶向肝脏中的非实质细胞。
