Advertisement

Specificity of Human Glucosylceramide ß-Glucosidase Towards Structurally Modified Glucosylceramides in a Liposomal Assay-System

  • Francesco Sarmientos
  • Günter Schwarzmann
  • Konrad Sandhoff
Part of the NATO ASI Series book series (NSSA, volume 116)

Abstract

Glycosphingolipids are the most abundant glycolipids in the plasma membrane of animal tissues. Their degradation occurs in lysosomes, where specific hydrolytic enzymes cut off the sugar moieties sequentially from the non-reducing end. All higher glycosphingolipids are finally hydrolyzed to glucosylceramide, which can be further degraded, via ceramide, to sphingosine. The degradation of glucosylceramide is accomplished by a membrane-associated enzyme, the glucosylceramide ß-glucosidase (EC 3.2.1.45), which hydrolyzes the membrane-bound sphingolipid to ceramide and glucose. This enzyme is defective in various forms of Gaucher’s disease (1,2) with consequent storage of glucosylceramide, primarily in the lysosomes of the reticuloendothelial system.

Keywords

Enzyme Replacement Therapy Phosphatidic Acid Sodium Taurocholate Tocopherol Acetate Amphiphilic Cation 
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. Comm. 18: 221 (1965).CrossRefGoogle Scholar
  2. 2.
    A.D. Patrick, A deficiency of glucocerebrosidase in Gaucher’s diesease, Biochem. J. 95: 17 c (1965).Google Scholar
  3. 3.
    A.Maret, R. Salvayre, A. Negre and L. Douste-Blazy, Propriétés des formes moléculaires de la ß-glucosidase et de la B-glucocérébrosidase de rate humaine normale et de maladie de Gaucher, Eur. J. Biochm. 115: 455 (1981).CrossRefGoogle Scholar
  4. 4.
    A.M. Vaccaro, T. Kobayashi and K. Suzuki, Comparison of synthetic and natural glucosylceramides as substrate for glucosylceramidase assay, Clin. Chim. Acta 118: 1 (1982).CrossRefGoogle Scholar
  5. 5.
    A.M. Vaccaro, M. Muscillo and K. Suzuki, Effect of hydrogenation of glucosyl-and galactosylceramide on their enzymatic hydrolysis, Clin. Chim. Acta 131: 1 (1983).CrossRefGoogle Scholar
  6. 6.
    G.A. Grabowski, S. Gatt, J. Kruse and R.J. Desnick, Human lysosomal B-glucosidase: kinetic characterization of the catalytic, aglycon, and hydrophobic binding sites, Arch. Biochm. Biophys. 231: 144 (1984).CrossRefGoogle Scholar
  7. 7.
    F.S. Furbish, H.E. Blair, J. Shiloach, P.G. Pentchev and R.O. Brady, Enzyme replacement therapy in Gaucher’s disease: large-scale purification of glucocerebrosidase suitable for human administration, Proc. Natl. Acad. Sci. USA 74: 3560 (1977).PubMedCrossRefGoogle Scholar
  8. 8.
    F.Sarmientos, G. Schwarzmann and K. Sandhoff, Specificity of human glucosylceramide B-glucosidase towards structurally modified glucosylceramides in a detergent-free assay-system, submitted.Google Scholar
  9. 9.
    M.W. Ho, J.S. O’Brien, N.S. Radin and J.S. Erickson, Glucocerebrosidase: reconstitution of activity from macromolecular components, Biochem. J. 131: 173 (1973).PubMedGoogle Scholar
  10. 10.
    S.P. Peters, P. Coyle, C.J. Coffee, R.H. Glew, M.S. Kuhlenschmidt, L. Rosenfeld and Y.C. Lee, Purification and properties of a heat-stable glucocerebrosidase activating factor from control and Gaucher spleen, J. Biol. Chem. 252: 563 (1977).PubMedGoogle Scholar
  11. 11.
    S.S. Jyer, S.L. Berent and N.S. Radin, The cohydrolases in human spleen that stimulate glucosylceramide B-glucosidase, Biochem. Biophys. Acta 748: 1 (1983).CrossRefGoogle Scholar
  12. 12.
    A.M. Vaccaro, M. Muscillo, E. Gallozzi, R. Salvioli, M. Tatti and K. Suzuki, An endogenous activator protein in human placenta for enzymatic degradation of glucosylceramide, Biochem. Biophys. Acta 836: 157 (1985).CrossRefGoogle Scholar
  13. 13.
    K.Sandhoff, Function and relevance of activator proteins for glycolipid degradation, in: “Molecular basis of lysosomal storage disorders”, J.A. Barranger and R.O. Brady, eds., Academic Press, Washington (1984).Google Scholar
  14. 14.
    H.-J. Kytzia and K. Sandhoff, Evidence for two different active sites on human hexosaminidase A. Interaction of GM2 activator protein with hexosaminidase A, J. Biol. Chem. 260: 7588 (1985).Google Scholar
  15. 15.
    E. Mehl and H. Jatzkewitz, Eine Cerebrosidsulfatase aus Schweineniere, Hoppe-Seyler’s Z. Physiol. Chem. 339: 260 (1964).CrossRefGoogle Scholar
  16. 16.
    G. Fischer and H. Jatzkewitz, The activator of cerebroside-sulphatase. A model of the activation, Biochim. Biophys. Acta 528: 69 (1978).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Francesco Sarmientos
    • 1
  • Günter Schwarzmann
    • 1
  • Konrad Sandhoff
    • 1
  1. 1.Institut für Organische Chemie und BiochemieUniversität BonnBonn 1Germany

Personalised recommendations