Lysosomal multienzyme complex: biochemistry, genetics, and molecular pathophysiology

Prog Nucleic Acid Res Mol Biol. 2001;69:81-114. doi: 10.1016/s0079-6603(01)69045-7.


Lysosomal enzymes sialidase (alpha-neuraminidase), beta-galactosidase, and N-acetylaminogalacto-6-sulfate sulfatase are involved in the catabolism of glycolipids, glycoproteins, and oligosaccharides. Their functional activity in the cell depends on their association in a multienzyme complex with lysosomal carboxypeptidase, cathepsin A. We review the data suggesting that the integrity of the complex plays a crucial role at different stages of biogenesis of lysosomal enzymes, including intracellular sorting and proteolytic processing of their precursors. The complex plays a protective role for all components, extending their half-life in the lysosome from several hours to several days; and for sialidase, the association with cathepsin A is also necessary for the expression of enzymatic activity. The disintegration of the complex due to genetic mutations in its components results in their functional deficiency and causes severe metabolic disorders: sialidosis (mutations in sialidase), GM1-gangliosidosis and Morquio disease type B (mutations in beta-galactosidase), galactosialidosis (mutations in cathepsin A), and Morquio disease type A (mutations in N-acetylaminogalacto-6-sulfate sulfatase). The genetic, biochemical, and direct structural studies described here clarify the molecular pathogenic mechanisms of these disorders and suggest new diagnostic tools.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carboxypeptidases / chemistry
  • Carboxypeptidases / genetics
  • Carboxypeptidases / physiology
  • Carboxypeptidases A
  • Cell Membrane / enzymology
  • Chondroitinsulfatases / chemistry
  • Chondroitinsulfatases / genetics
  • Chondroitinsulfatases / physiology
  • Gangliosidosis, GM1 / enzymology
  • Gangliosidosis, GM1 / genetics
  • Humans
  • Lysosomal Storage Diseases / enzymology
  • Lysosomal Storage Diseases / genetics
  • Lysosomes / enzymology*
  • Models, Molecular
  • Mucolipidoses / enzymology
  • Mucolipidoses / genetics
  • Mucopolysaccharidosis IV / enzymology
  • Mucopolysaccharidosis IV / genetics
  • Multienzyme Complexes / chemistry*
  • Multienzyme Complexes / genetics*
  • Multienzyme Complexes / physiology
  • Neuraminidase / chemistry
  • Neuraminidase / genetics
  • Neuraminidase / physiology
  • Protein Conformation
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology
  • beta-Galactosidase / chemistry
  • beta-Galactosidase / genetics
  • beta-Galactosidase / physiology


  • Multienzyme Complexes
  • Receptors, Cell Surface
  • elastin-binding proteins
  • Chondroitinsulfatases
  • GALNS protein, human
  • Neuraminidase
  • beta-Galactosidase
  • Carboxypeptidases
  • Carboxypeptidases A