title: Lysosomal high molecular weight multienzyme complex.
abstract: 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.
authors.affiliation: Department of Biology, Medical Academy of Białystok, Poland. halost@amb.edu.pl
authors.forename: Halina
authors.initials: H
authors.lastname: Ostrowska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Krukowska
authors.forename: Joanna
authors.initials: J
authors.lastname: Kalinowska
authors.forename: Mirosława
authors.initials: M
authors.lastname: Orłowska
authors.forename: Ilona
authors.initials: I
authors.lastname: Lengiewicz
mesh_terms: D043402:Cathepsin A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002811:Chondroitinsulfatases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000201:enzymology / Q000235:genetics; D008247:Lysosomes / Q000201:enzymology*; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009439:Neuraminidase / Q000737:chemistry / Q000378:metabolism; D001616:beta-Galactosidase / Q000737:chemistry / Q000378:metabolism
chemical_list: D009097:Multienzyme Complexes; D002811:Chondroitinsulfatases; C102295:GALNS protein, human; D009439:Neuraminidase; D001616:beta-Galactosidase; D043402:Cathepsin A