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Intracellular processing and maturation of mutant gene products in hereditary beta-galactosidase deficiency (beta-galactosidosis).
- Source :
-
Human genetics [Hum Genet] 1994 Feb; Vol. 93 (2), pp. 109-14. - Publication Year :
- 1994
-
Abstract
- Heterogeneous patterns of biosynthesis, posttranslational processing, and degradation were demonstrated for mutant enzymes in three clinical forms of beta-galactosidase deficiency (beta-galactosidosis): juvenile GM1-gangliosidosis, adult GM1-gangliosidosis, and Morquio B disease. The precursor of the mutant enzyme in adult GM1-gangliosidosis was not phosphorylated, and only a small portion of the gene product reached the lysosomes. The enzyme in Morquio B disease was normally processed and transported to lysosomes, but its catalytic activity was low. A common gene mutation in juvenile GM1-gangliosidosis (R201C) produced an enzyme protein that did not aggregate with protective protein in the lysosome, and was rapidly degraded by thiol proteases. This abnormal turnover was similar to that for the normal but dissociated beta-galactosidase in galactosialidosis. Protease inhibitors restored the enzyme activity in fibroblasts of this clinical form. A possible therapeutic approach is discussed for this specific type of enzyme deficiency.
- Subjects :
- Adult
Cell Line, Transformed
Cells, Cultured
Centrifugation, Density Gradient
Child, Preschool
Female
Fibroblasts enzymology
Gangliosidosis, GM1 genetics
Gene Expression
Humans
Male
Mucopolysaccharidosis IV genetics
Neuraminidase metabolism
Phosphorylation
Proteins
Subcellular Fractions
beta-Galactosidase metabolism
Gangliosidosis, GM1 enzymology
Mucopolysaccharidosis IV enzymology
Protein Processing, Post-Translational genetics
beta-Galactosidase deficiency
beta-Galactosidase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0340-6717
- Volume :
- 93
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 8112731
- Full Text :
- https://doi.org/10.1007/BF00210592