Tags

Type your tag names separated by a space and hit enter

Defects in synthesis, phosphorylation, and maturation of acid alpha-glucosidase in glycogenosis type II.
J Biol Chem. 1985 Jul 15; 260(14):8336-41.JB

Abstract

Glycogenosis type II is an inherited lysosomal storage disease with acid alpha-glucosidase deficiency as the primary defect. Using cultured skin fibroblasts, we have studied the biosynthesis of acid alpha-glucosidase in clinically different forms of this disease. Three unrelated patients were identified (one with an infantile, one with a juvenile, and one with an adult form of the disease) producing normal quantities of the 110-kDa precursor form of acid alpha-glucosidase. However, post-translational modification to mature 76-kDa enzyme protein was either completely deficient or extremely inefficient. No abnormalities were observed in glycosylation of the mutant precursors, as measured by the incorporation of [3H]mannose, but phosphorylation was only detectable for the precursor synthesized by fibroblasts from the juvenile patient. In three other patients (one with a juvenile and two with adult forms of glycogenosis type II) apparently reduced synthesis of precursor protein was observed, but the processing to mature enzyme seemed to be undisturbed. Finally, neither precursor nor mature forms of acid alpha-glucosidase were detectable in one particular case of infantile glycogenosis type II. The studies reveal an unexpected degree of genetic heterogeneity in this disease and identify various mutants which could be of importance to further elucidate the biosynthetic events during lysosomal enzyme formation.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

3159730

Citation

Reuser, A J., et al. "Defects in Synthesis, Phosphorylation, and Maturation of Acid Alpha-glucosidase in Glycogenosis Type II." The Journal of Biological Chemistry, vol. 260, no. 14, 1985, pp. 8336-41.
Reuser AJ, Kroos M, Oude Elferink RP, et al. Defects in synthesis, phosphorylation, and maturation of acid alpha-glucosidase in glycogenosis type II. J Biol Chem. 1985;260(14):8336-41.
Reuser, A. J., Kroos, M., Oude Elferink, R. P., & Tager, J. M. (1985). Defects in synthesis, phosphorylation, and maturation of acid alpha-glucosidase in glycogenosis type II. The Journal of Biological Chemistry, 260(14), 8336-41.
Reuser AJ, et al. Defects in Synthesis, Phosphorylation, and Maturation of Acid Alpha-glucosidase in Glycogenosis Type II. J Biol Chem. 1985 Jul 15;260(14):8336-41. PubMed PMID: 3159730.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Defects in synthesis, phosphorylation, and maturation of acid alpha-glucosidase in glycogenosis type II. AU - Reuser,A J, AU - Kroos,M, AU - Oude Elferink,R P, AU - Tager,J M, PY - 1985/7/15/pubmed PY - 1985/7/15/medline PY - 1985/7/15/entrez SP - 8336 EP - 41 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 260 IS - 14 N2 - Glycogenosis type II is an inherited lysosomal storage disease with acid alpha-glucosidase deficiency as the primary defect. Using cultured skin fibroblasts, we have studied the biosynthesis of acid alpha-glucosidase in clinically different forms of this disease. Three unrelated patients were identified (one with an infantile, one with a juvenile, and one with an adult form of the disease) producing normal quantities of the 110-kDa precursor form of acid alpha-glucosidase. However, post-translational modification to mature 76-kDa enzyme protein was either completely deficient or extremely inefficient. No abnormalities were observed in glycosylation of the mutant precursors, as measured by the incorporation of [3H]mannose, but phosphorylation was only detectable for the precursor synthesized by fibroblasts from the juvenile patient. In three other patients (one with a juvenile and two with adult forms of glycogenosis type II) apparently reduced synthesis of precursor protein was observed, but the processing to mature enzyme seemed to be undisturbed. Finally, neither precursor nor mature forms of acid alpha-glucosidase were detectable in one particular case of infantile glycogenosis type II. The studies reveal an unexpected degree of genetic heterogeneity in this disease and identify various mutants which could be of importance to further elucidate the biosynthetic events during lysosomal enzyme formation. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/3159730/Defects_in_synthesis_phosphorylation_and_maturation_of_acid_alpha_glucosidase_in_glycogenosis_type_II_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=3159730 DB - PRIME DP - Unbound Medicine ER -