Characterization of the molecular defect in infantile and adult acid alpha-glucosidase deficiency fibroblasts.

Beratis, Nicholas G.; Labadie, Gundula U; Hirschhorn, Kurt

doi:10.1172/jci109247

Cited by 51 publications

(18 citation statements)

References 25 publications

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“…As indicated in table I, the residual activity tended to be higher in patients with the juvenile phenotype than in those with the infantile phenotype, and higher in pa tients with the adult phenotype than in those with the juvenile form of the disease. Nev ertheless, there was considerable overlap, as also found earlier by others [13,14], The aa-Glucosidase, like other lysosomal en zymes, is a glycoprotein [22], Hasilik and Neufeld [15,16] were the first to show by means of metabolic labelling studies with radioactively labelled amino acids, mannose and phosphate that the enzyme is synthe sized as a large precursor containing phosphorylated mannose residues and that the precursor is proteolytically converted to the mature form of the enzyme. The precursor has a molecular weight of 110 kilodaltons and is converted via intermediate forms of 105 and 95 kilodaltons to the 76-kilodalton mature protein and, after longer periods, to a 70-kilodalton form [11,19,21,23].…”

Section: Biosynthesis Of A-glucosidase In Cultured Skin Fibroblastssupporting

confidence: 81%

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α-Glucosidase Deficiency (Pompe’s Disease)

Tager

Elferink²,

Reuser³

et al. 1987

Enzyme

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α-Glucosidase is deficient (< 30% of control) in Pompe’s disease, but the extent of the deficiency does not always correlate with the severity of the clinical symptoms. The defects that lead to a deficiency of a-glucosidase include synthesis of catalytically inactive protein, absence of mRNA for the enzyme, decreased synthesis of the precursor, lack of phosphorylation of the precursor, impaired conversion of the precursor to the mature enzyme and synthesis of unstable precursor. A single type of defect can lead to different clinical phenotypes. The precursor of α-glucosidase is present in the brush border of the polarized epithelial cells of small intestine and kidney and is secreted into urine.

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Section: Biosynthesis Of A-glucosidase In Cultured Skin Fibroblastssupporting

confidence: 81%

“…clinical symptoms in Pompe's disease does not always correlate with the amount of re sidual a-glucosidase activity in the patients [13,14]. Thus other factors must play a role in determining the clinical course of the dis ease.…”

Section: Introductionmentioning

confidence: 99%

α-Glucosidase Deficiency (Pompe’s Disease)

Tager

Elferink²,

Reuser³

et al. 1987

Enzyme

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“…Enzyme uptake and stability studies were also carried out in 24-well culture plates. 5-15 Units of acid a-glucosidase, purified from control cells or fibroblasts from patients with adult forms of glycogenosis type II (as in [5]) were added overnight to the medium (500 t~l) of acceptor cells. For this purpose we used fibroblasts from patients with the infantile form of glycogenosis type II, without any detectable acid a-glucosidase activity.…”

Section: Published By Elsevier Biomedical Pressmentioning

confidence: 99%

Adult forms of glycogenosis type II

Reuser

Kroos

1982

FEBS Letters

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The activity of acid α‐glucosidase in cultured fibroblasts from adult patients with the lysosomal storage disease glycogenosis type II is only 10% of normal. A normal activity per molecule is found for the mature as well as for the precursor form of acid α‐glucosidase in adult mutant fibroblasts. Excessive lysosomal breakdown of mature enzyme purified from mutant fibroblasts and taken up by acceptor cells does not occur. However, the NH4Cl‐stimulated secretion of a precursor form of acid α‐glucosidase by adult mutant fibroblasts is markedly reduced. The results are indicative of a defect during the production of acid α‐glucosidase.

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“…The peroxidase reaction mixture stained the gel brown; rockets appeared white against the brown background. Crossed immunoisoelectric gels were stained with Coomassie Brilliant Blue R-250 and destained as previously described (31).…”

Section: Immunologic Studiesmentioning

confidence: 99%