Molecular defect in combined beta-galactosidase and neuraminidase deficiency in man.
AUTOR(ES)
D'Azzo, A
RESUMO
In normal human fibroblasts, an enzymically active 85,000-dalton precursor form of beta-galactosidase is processed, via a number of intermediates, into a mature 64,000-dalton form. In addition there is an enzymically inactive 32,000-dalton component and its 54,000-dalton precursor. In fibroblasts from patients with a combined deficiency of beta-galactosidase and neuraminidase these last two components are absent and hardly any mature beta-galactosidase can be demonstrated. Nevertheless, in the mutant fibroblasts, precursor beta-galactosidase is synthesized and processed normally. The excessive intralysosomal degradation that is responsible for the deficiency of mature beta-galactosidase can be partially corrected by addition of the protease inhibitor leupeptin, which results in the accumulation of 85,000-dalton precursor beta-galactosidase and of a partially processed 66,000-dalton form. When mutant cells were grown in the presence of a "corrective factor" purified from the medium of NH4Cl-stimulated cell cultures, both beta-galactosidase and neuraminidase activities were restored to low control levels. The immunoprecipitation pattern was completely normal after addition of the corrective factor, and mature 64,000-dalton beta-galactosidase accumulated in the mutant fibroblasts. We propose that the combined beta-galactosidase/neuraminidase deficiency is caused by a defective 32,000-dalton glycoprotein which is normally required to protect beta-galactosidase and neuraminidase against excessive intralysosomal degradation and to give these enzymes their full hydrolytic activity.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=346709Documentos Relacionados
- Mechanism of the rel defect in beta-galactosidase synthesis.
- Molecular basis of beta-galactosidase alpha-complementation.
- Globoid Cell Leukodystrophy: Deficiency of Lactosyl Ceramide Beta-Galactosidase
- Vaccinia virus recombinants expressing an 11-kilodalton beta-galactosidase fusion protein incorporate active beta-galactosidase in virus particles.
- Concentrated beta-galactosidase and cell permeabilization from Saccharomyces fragilis IZ 275 for beta-galactosidase activity in the hydrolysis of lactose