Ostrowska Halina, Krukowska Katarzyna, Kalinowska Joanna, Orłowska Mirosława, Lengiewicz Ilona
Department of Biology, Medical Academy of Białystok, Poland.
Cell Mol Biol Lett. 2003;8(1):19-24.
Three acidic glycosidases: beta-galactosidase (beta-GAL, EC 3.2.1.23), alpha-neuraminidase (NEUR, sialidase, EC 3.2.1.18), N-acetylaminogalacto-6-sulfate sulfatase (GALNS, EC 3.1.6.4) and serine carboxypepidase cathepsin A (EC 3.4.16.1) form a functional high molecular weight complex in the lysosomes. The major constituent of this complex is cathepsin A, the so-called "lysosomal protective protein" (PPCA). By forming a multienzyme complex, it protects the glycosidases from rapid intralysosomal proteolysis, and it is also required for the intracellular sorting and proteolytic processing of their precursors. In man, a deficiency of cathepsin A leads to a combined deficiency of beta-GAL and NEUR activities, called "galactosialidosis". Multiple mutations identified in the cathepsin A gene are the molecular basis of this lysosomal storage disease. This review describes the structural organization of the lysosomal high molecular weight multienzyme complex and the importance of the protective protein/cathepsin A in physiology and pathology.
β-半乳糖苷酶（β-GAL，EC 3.2.1.23）、α-神经氨酸酶（NEUR，唾液酸酶，EC 3.2.1.18）、N-乙酰氨基半乳糖-6-硫酸酯硫酸酯酶（GALNS，EC 3.1.6.4）和丝氨酸羧肽酶组织蛋白酶A（EC 3.4.16.1）在溶酶体中形成一种功能性高分子量复合物。该复合物的主要成分是组织蛋白酶A，即所谓的“溶酶体保护蛋白”（PPCA）。通过形成多酶复合物，它保护糖苷酶免受溶酶体内快速的蛋白水解作用，并且其前体的细胞内分选和蛋白水解加工也需要它。在人类中，组织蛋白酶A的缺乏会导致β-GAL和NEUR活性的联合缺乏，称为“半乳糖唾液酸贮积症”。在组织蛋白酶A基因中鉴定出的多个突变是这种溶酶体贮积病的分子基础。本综述描述了溶酶体高分子量多酶复合物的结构组织以及保护蛋白/组织蛋白酶A在生理和病理中的重要性。
