Advertisement

Molecular Forms, Biosynthesis and Maturation of Glucocerebrosidase, a Membrane-Associated Lysosomal Enzyme Deficient in Gaucher Disease

  • J. M. Tager
  • J. M. F. G. Aerts
  • L. M. V. Jonsson
  • G. J. Murray
  • S. van Weely
  • A. Strijland
  • E. I. Ginns
  • A. J. J. Reuser
  • A. W. Schram
  • J. A. Barranger
Part of the NATO ASI Series book series (NSSA, volume 116)

Abstract

Glucocerebrosidase is a membrane-associated lysosomal enzyme. Its physiological funtion is to catalyse the hydrolysis of the β-glucosidic bonds in the glycosphingolipid glucocerebroside. There is a deficiency of the enzyme in Gaucher disease, which leads to excessive accumulation of glucocerebroside in cells of the reticuloendothelial system 1,2. Three phenotypes of Gaucher disease are recognized: type 1, the adult, nonneuronopathic form; type 2, the acute, neuronopathic form; and type 3, the subacute, neuronopathic form3. Attempts have been made to correlate the clinical phenotype with stored lipid, residual activity of the enzyme, molecular forms seen after isoelectric focussing, enzymological parameters of the residual enzyme activity, or extent of stimulation of delipidated splenic glucocerebrosidase by acidic phospholipids or a heat-stable “activator protein”, but no clear, consistent picture has emerged from the results of these studies (reviewed in refs. 4–7).

Keywords

Lysosomal Enzyme Gauche Disease Gauche Disease Type Gauche Disease Patient Isoelectric Focussing 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    R. O. Brady, J. N. Kanfer and D. Shapiro, Metabolism of glucocerebrosides. II. Evidence of an enzymatic deficiency in Gaucher’s disease., Biochem. Biophys. Res. Commun 18: 221 (1965)PubMedCrossRefGoogle Scholar
  2. 2.
    A. D. Patrick, A deficiency of glucocerebrosidase in Gaucher’s disease., Biochem. J. 97: 17c (1965)Google Scholar
  3. 3.
    R. O. Brady and J.A. Barranger, Glucosylceramide lipidosis: Gaucher’s disease., in: The Metabolic Basis of Inherited Disease (J. B. Stanbury, J. B. Wijngaarden, D. S. Frederickson, J. L. Goldstein and M. S. Brown, eds.) p. 842 McGraw-Hill, New York (1983)Google Scholar
  4. 4.
    E. I. Ginns, R. O. Brady, S. Pirrucello, C. Moore, S. Sorrell, F. S. Furbish, G. J. Murray, J. M. Tager and J. A. Barranger, Mutations of glucocerebrosidase. Discrimination of neurologic and non-neurologic phenotypes of Gaucher disease., Proc. Natl. Acad. Sci. USA 79: 5067 (1983)Google Scholar
  5. 5.
    E. I. Ginns, F. P. W. Tegelaers, R. Barneveld, H. Galjaard, A. J. J. Reuser, R. O. Brady, J. M. Tager and J. A. Barranger, Determination of Gaucher’s disease phenoptypes with monoclonal antibodies. Clin. Chim. Acta 131: 283 (1983)PubMedCrossRefGoogle Scholar
  6. 6.
    F. Y. M. Choy, Gaucher disease: the effects of phosphatidylserine on glucocerebrosidase from normal and Gaucher fibroblasts., Hum. Genet. 67: 432 (1984)PubMedCrossRefGoogle Scholar
  7. 7.
    J. M. F. G. Aerts, W. E. Donker-Koopman, M. K. Van der Vliet, L. M. V. Jonsson, E. I. Ginns, G. J. Murray, J. A. Barranger, J. M. Tager and A. W. Schram, The occurrence of two immunologically distinguishable ß-glucocerebrosidases in human spleen., Eur. J. Biochem. 150: 565 (1985)PubMedCrossRefGoogle Scholar
  8. 8.
    A. H. Erickson, E. I. Ginns and J. A. Barranger, Biosynthesis of the lysosomal enzyme glucocerebrosidase., J. Biol. Chem. in press (1985)Google Scholar
  9. 9.
    J. M. van Dongen, R. Willemsen, E. I. Ginns, H. J. Sips, J. M. Tager, J. A. Barranger and A. J. J. Reuser, The subcellular localization of soluble and membrane-bound lysosomal enzymes in I-cell fibroblasts: a comparative immunocytochemical study., Eur. J. Cell Biol. in press (1985)Google Scholar
  10. 10.
    R. Willemsen, J. M. van Dongen, E. I. Ginns, H. J. Sips, A. W. Schram, J. M. Tager, J. A. Barranger and A. J. J. Reuser, Unpublished observations Google Scholar
  11. 11.
    E. I. Ginns, P. V. Choudary, B. M. Martin, S. Winfield, B. Stubbefield, J. Mayor, D. Merkle-Lehman, G. J. Murray, L. A. Bowers and J. A. Barranger, Isolation of cDNA clones for human ß-glucocerebrosidase using the Xgtll expression system., Biochem. Biophys. Res. Commun. 123: 574 (1984)PubMedCrossRefGoogle Scholar
  12. 12.
    S. P. Peters, P. Coyle and R. H. Glew, Differentiation of ß-glucocerebrosidase from ß-glucosidase in human tissues using sodium taurocholate., Arch. Biochem. Biophys 175: 569 (1976)PubMedCrossRefGoogle Scholar
  13. 13.
    L. B. Daniels, P.J. Coyle, Y.-B. Chiao, R. H. Glew and R. S. Labow, Purification and characterization of a cytosolic broad specificity ß-glucosidase from human liver., J. Biol. Chem. 256: 13004 (1981)PubMedGoogle Scholar
  14. 14.
    A. Maret, R. Salvayre, A. Negre and L. Douste-Blazy, Separation par electrofocalisation des formes moleculaires de la ß-glucosidase splenique chez le sujet normal et au cours de la maladie de Gaucher, Biomedicine 33: 82 (1980)PubMedGoogle Scholar
  15. 15.
    E. I. Ginns, R. 0. Brady, D. W. Stowens, F. S. Furbish and J. A. Barranger, A new group of glucocerebrosidase isoenzymes found in human white blood cells., Biochem. Biophys. Res. Commun 97: 1103 (1980)PubMedCrossRefGoogle Scholar
  16. 16.
    A. Maret, R. Salvayre, A. Negre and L. Douste-Blazy, Propriétes des formes moleculaires de la ß-glucocerebrosidase de rate humaine normale et de maladie de Gaucher., Eur. J. Biochem. 115: 455 (1981)PubMedCrossRefGoogle Scholar
  17. 17.
    E. Beutler, W. Kuhl and J. Sorge, Cross reacting material in Gaucher’s disease fibrolasts., Proc. Natl. Acad. Sci. USA 81: 6506 (1985)CrossRefGoogle Scholar
  18. 18.
    J. M. F. G. Aerts, W. E. Donker-Koopman, M. Koot, E. M. BrouwerKelder, G. J. Murray, J. A. Barranger, J. M. Tager and A. W. Schram, Forms of glucocerebrosidase present in tissues and urine., this volumeGoogle Scholar
  19. 19.
    S. P. Peters, P. Coyle, C. J. Coffee, R. H. Glew, M. S. Kuhlenschmidt, L. Rosenfeld and Y.-C. Lee, Isolation of heat-stable glucocerebrosidase activators from the spleens of three variants of Gaucher’s disease., J. Biol. Chem. 252: 563 (1977)PubMedGoogle Scholar
  20. 20.
    A. W. Schram, L. M. V. Jonsson, G. J. Murray and A. Strijland, Unpublished observations.Google Scholar
  21. 21.
    A. Hasilik, A. Waheed and K. von Figura, Enzymatic phosphorylation of lysosomal enzymes in the presence of UDP-N-acetylglucosamine. Absence of the activity in I-cell fibroblasts., Biochem. Biophys. Res. Commun 98: 761 (1981)PubMedCrossRefGoogle Scholar
  22. 22.
    M. L. Reitman, A. Varki and S. Kornfeld, Fibroblasts from patients with I-cell disease and pseudo-Hurler polydystrophy are deficient in uridine 5′-diphosphate-N-acetylglucosamine: glycoprotein N-ace-tylglucosaminylphosphotransferase activity., J. Clin. Invest. 67: 1574 (1981)CrossRefGoogle Scholar
  23. 23.
    T. Kudah, M. A. Velkoff and D. A. Wenger, Uptake and metabolism of radioactively labelled sphingomyelinase in cultured skin fibroblasts from controls and patients with Niemann-Pick disease and other lysosomal storage diseases., Biochim. Biophys. Acta 754: 82 (1984)Google Scholar
  24. 24.
    G. J. Murray, L. M. V. Jonsson, S. Sorrell, E. I. Ginns, J. M. Tager, A. W. Schram and J. A. Barranger, Phosphorylation of glucocerebrosidase: lysosomal enzyme processing independent of the mannose 6-phosphate receptor mediated pathway., Abstr. 13th Intern. Congr. Biochem, Amsterdam, p. 733 (1985)Google Scholar
  25. 25.
    L. M. V. Jonsson, G. J. Murray, A. Strijland, J. M. F. G. Aerts, E. I. Ginns, J. A. Barranger, J. M. Tager and A. W. Schram, Biosynthesis and maturation of glucocerebrosidase in relation to Gaucher’s disease., Abstr. 13th Intern. Congr. Biochem, Amsterdam, p. 185 (1985)Google Scholar
  26. 26.
    J. N. Kanfer, B. Legler, J. Sullivan, S. S. Raghavan and R. A. Mumford, The Gaucher mouse., Biochem. Biophys. Res. Commun. 67: 85 (1975)PubMedCrossRefGoogle Scholar
  27. 27.
    S. Tsuji„ P. V. Choudary, B. M. Martin, S. Winfield, J. A. Barranger and E. I. Ginns, Nucleotide sequence of cDNA containing the complete coding sequence of human lysosomal glucocerebrosidase., J. Biol. Chem., in press (1985)Google Scholar
  28. 28.
    P. D. Choudary, M. Horowitz, J.A. Barranger and E.I. Ginns, Gene transfer and expression of active human glucocerebrosidase in mammalian cell cultures., Proceedings 6th Annual Congress for Recombinant DNA Research, Baltimore, in press (1986).Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • J. M. Tager
    • 1
  • J. M. F. G. Aerts
    • 1
  • L. M. V. Jonsson
    • 1
    • 2
  • G. J. Murray
    • 2
  • S. van Weely
    • 1
  • A. Strijland
    • 1
  • E. I. Ginns
    • 2
  • A. J. J. Reuser
    • 3
  • A. W. Schram
    • 1
  • J. A. Barranger
    • 2
  1. 1.Laboratory of BiochemistryUniversity of AmsterdamAmsterdamThe Netherlands
  2. 2.Clinical Investigations and Therapeutics Section and Molecular and Medical Genetics Section, Developmental and Metabolic Neurology BranchNational Institute of Neurologi­cal and Communicative Disorders and Stroke, National Institutes of HealthBethesdaUSA
  3. 3.Department of Cell Biology and GeneticsErasmus UniversityRotterdamThe Netherlands

Personalised recommendations