Advertisement

Inhibitors of β-Glucosidases of Animal Tissues

  • Norman S. Radin
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 101)

Abstract

Our first effort in the field of glucocerebroside manip­ulation stemmed directly from an observation by one of this meeting’s sponsors, Dr. Shimon Gatt. Dr. Gatt had purified glucocerebrosidase from brain to a certain degree and, in studying its properties, found that sphingosine produced good inhibition (1). It seemed likely that we could increase the strength and specificity of the effect by adding a glucosyl moiety to the sphingosine. John Erickson and I prepared glu­cosyl sphingosine from Gaucher spleen cerebroside and found that it was indeed a stronger inhibitor (2). When the com­pounds were tested with rat spleen cerebrosidase at the 0.3 mM level, sphingosine produced 59% inhibition and the glucoside produced 75% inhibition. Galactosyl sphingosine, the β-galac­toside made from brain cerebroside, had no effect at all, showing that the sugar residue was very important.

Keywords

Glucose Moiety Glucosidase Activity Glucosidase Inhibitor Gauche Patient Glucosyl Moiety 
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.
    Gatt, S. Biochem. J. 101: 687–691, 1966.PubMedGoogle Scholar
  2. 2.
    Erickson, J.S. and Radins N.S. J. Lipid Res. 14: 133–137, 1973.PubMedGoogle Scholar
  3. 3.
    Alberty, R.A. and Massey, V. Biochim. Biophys. Acta 13: 347–353, 1954.PubMedCrossRefGoogle Scholar
  4. 4.
    Arora, R.C., Lin, Y.-N, and Radin, N.S. Arch. Bióchem. Biophys. 156: 77–83, 1973.PubMedCrossRefGoogle Scholar
  5. 5.
    Hyun, J.C., Misra, R.S., Greenblatt, D., and Radin, N.S. Arch. Biochem. Biophys. 166: 382–389, 1975.PubMedCrossRefGoogle Scholar
  6. 6.
    Vunnam,’R.R. and Radin, N.S., unpublished work.Google Scholar
  7. 7.
    Mellor, J.D. and Layne, D.S. J. Biol. Chem. 246: 4377 4380, 1971.Google Scholar
  8. 8.
    Mumford, R.A., Raghavan, S.S., and Kanfer, J.N. J. Neurochem. 27: 943–948, 1976.PubMedCrossRefGoogle Scholar
  9. 9.
    Abrahams, H.E. and Robinson, D. Biochem. J. 111: 749–755, 1969.PubMedGoogle Scholar
  10. 10.
    Leese, H.J. and Semenza, G. J. Biol. Chem. 248: 8170–8173, 1973.PubMedGoogle Scholar
  11. 11.
    Brady, R.O., Gal, A.E., Kanfer, J.N., and Bradley, R.M. J. Biol. Chem. 240: 3766–3770, 1965.PubMedGoogle Scholar
  12. 12.
    Weinreb, N.J. and Brady, R.O. Methods Enzymol. 28, 830–834 (1972). V. Ginsburg, ed., Academic Press, N.Y.Google Scholar
  13. 13.
    Kanfer, J.N., Stein, M., and Spielvogel, C. Sphingolipids, Sphingolipidoses, and Allied Disorders, 225–236, 1972. B.W. Volk and S.M. Aronson, eds., Plenum Press, N.Y.Google Scholar
  14. 14.
    Raychaudhuri, C. and Desai, I.D. Int. J. Biochem. 3: 684690, 1972.Google Scholar
  15. 15.
    Glew, R.H., Peters, S.P., and Christopher, A.R. Biochim. Biophys. Acta 422: 179–199, 1976.PubMedCrossRefGoogle Scholar
  16. 16.
    Klibansky, Ch., Hoffman, J., Zaizov, R., and Matoth, Y. Biomed. 20: 24–30, 1974.Google Scholar
  17. 17.
    Conchie, J. and Levvy, G.A. Biochem. J. 65: 389, 1957.PubMedGoogle Scholar
  18. 18.
    Lai, H.-Y.L., and Axelrod, B. Biochem. Biophys. Res. Comm. 54: 463–468, 1973.PubMedCrossRefGoogle Scholar
  19. 19.
    Pentchev, P.G., Brady, R.O., Hibbert, S.R., Gal, A.E., and Shapiro, D. J. Biol. Chem. 248: 5256–5261, 1973.PubMedGoogle Scholar
  20. 20.
    Niwa, T., Inouye, S., Tsuruoka, T., Koaze, K., and Níida, T. Agric. Biol. Chem. 34: 966–968, 1970.CrossRefGoogle Scholar
  21. 21.
    Reese, E.T., Parrish, F.W., and Ettlinger, M. Carbohyd. Res. 18: 381–388, 1971.CrossRefGoogle Scholar
  22. 22.
    Kelemen, M.V. and Whelan, W.J. Arch. Biochem. Biophys. 117: 423–428, 1966.PubMedCrossRefGoogle Scholar
  23. 23.
    Shulman, M.L., Shiyan, S.D., and Khorlin, A. Ya. Biochim. Biophys. Acta 445: 169–181, 1976.PubMedCrossRefGoogle Scholar
  24. 24.
    Blonder, E., Klibansky, C., and deVries, A. Biochim. Biophys. Acta 431: 45–53, 1976.PubMedCrossRefGoogle Scholar
  25. 25.
    Peters, S.P. and Glew, R.H. Practical Enzymology of the Sphingolipidoses. Liss Publ. Co. 1977, in press.CrossRefGoogle Scholar
  26. 26.
    Ho, M.W. and Light, N.D. Biochem. J. 136: 821–823, 1973.PubMedGoogle Scholar
  27. 27.
    Legler, G. Z. Physiol. Chem. 345: 197–214, 1966.CrossRefGoogle Scholar
  28. 28.
    Legler, G. Z. Physiol. Chem. 349: 767–774, 1968.CrossRefGoogle Scholar
  29. 29.
    Bause, E. and Legler, G. Z. Physiol. Chem. 355: 438–442, 1974.CrossRefGoogle Scholar
  30. 30.
    Matoth, Y., Zaizov, R., Hoffman, J., and Klibansky, Ch. Israel J. Med. Sci. 10: 1023–1529, 1974.Google Scholar
  31. 31.
    Warren, K.R., Schafer, I.A., Sullivan, J.C., Petrellí, M., and Radin, N.S. J. Lipid Res. 17: 132–138, 1976.PubMedGoogle Scholar
  32. 32.
    Dawson, G., Stoolmiller, A.C., and Radin, N.S. J. Biol. Chem. 249: 4634–4646, 1974.Google Scholar
  33. 33.
    Berent, S.L. and Radin, N.S., unpublished work.Google Scholar
  34. 34.
    Tomino, S., Paigen, K., Tulsiani, D.R.P., and Touster, O. J. Biol. Chem. 250: 8503–8509, 1975.PubMedGoogle Scholar
  35. 35.
    Radin, N.S., Warren, K.R., Arora, R.C., Hyun, J.C., and Misra, R.S. Modification of Lipid Metabolism, 87–104, 1975: E.G. Perkins and L.A. Witting, eds., Academic Press, N.Y.Google Scholar
  36. 36.
    Kanfer, J.N.., Raghavan, S.S., Mumford, R.A., Sullivan, J., Spielvogel, S., Legler, G., Labow, R.S., Williamson, D.G., and Layne, D.S. Current Trends in Sphingolipidoses and Allied Disorders, 77–98, 1976. B.W. Volk and L. Schneck, eds., Plenum Press, N.Y.Google Scholar
  37. 37.
    Kanfer, J.N., Legler, G., Sullivan, J., Raghavan, S.S., and Mumford, R.A. Biochem. Biophys. Res. Commun. 67: 85–90, 1975.PubMedCrossRefGoogle Scholar
  38. 38.
    Hara, A. and Radin, N.S. Federation Proc. 36: 731, 1977.Google Scholar
  39. 39.
    Kampine, J.P., Kanfer, J.N., Gal, A.E., Bradley, R.M., and Brady, R.O. Biochim. Biophys. Acta 137: 135–139, 1967.PubMedCrossRefGoogle Scholar
  40. 40.
    Weinreb, N.J. Federation Proc. 35: 537, 1976.Google Scholar

Copyright information

© Plenum Press, New York 1978

Authors and Affiliations

  • Norman S. Radin
    • 1
  1. 1.Mental Health Research Institute & Department of Biological ChemistryThe University of MichiganAnn ArborUSA

Personalised recommendations