Inhibitors of xylose reductase from the yeast pichia stipitis

  • Steven R. Webb
  • Hung Lee


Several compounds were examined for their inhibitory effects on xylose reductase from the yeastPichia stipitis NRC 2548. Mercuric chloride, cupric chloride, menadione sodium bisulfite, and sodium bisulfite inhibited enzyme activity in a sigmoidal dose-dependent manner, whereas quercetin and rutin were observed to have nonsigmoidal dose-response curves. Diphenylhydantoin, hydantoin, and valproic acid had no effect on xylose reductase activity. Mercuric chloride was the most potent inhibitor tested, with an IC50 (the concentration that inhibited enzyme activity by 50%) of 4.7xl0-6M. Three distinct inhibition patterns were observed amongst selected inhibitors. Mercuric chloride and quercetin were noncompetitive inhibitors of xylose reductase with respect to substrate and cofactor. Sodium bisulfite was an uncompetitive inhibitor with respect to substrate and cofactor, whereas menadione sodium bisulfite was a competitive inhibitor with respect to substrate, but noncompetitive to the cofactor.

Index Entries

Aldose reductase inhibition xylose reductase D-xylose fermentation yeast 


  1. 1.
    Biely, P. (1985),Trends Biotechnol. 3, 286–290.CrossRefGoogle Scholar
  2. 2.
    Schneider, H., Wang, P. Y., Chan, Y. K., and Maleszka, R. (1981),Biotechnol. Lett. 3, 89–92.CrossRefGoogle Scholar
  3. 3.
    Slininger, P. J., Bothast, R. J., van Cauwenberge, J. E., and Kurtzmann, C. P. (1982),Biotechnol. Bioeng. 24, 371–384.CrossRefGoogle Scholar
  4. 4.
    Webb, S. R. and Lee, H. (1990),Biotechnol. Adv. 8, 685–697.CrossRefGoogle Scholar
  5. 5.
    Schneider, H., Lee, H., Barbosa, M., de F. S., Kubicek, C. P., and James, A. P. (1989),Appl. Environ. Microbiol. 55, 2877–2881.Google Scholar
  6. 6.
    Hagedorn, J. and Ciriacy, M. (1989),Curr. Genet. 16, 27–33.CrossRefGoogle Scholar
  7. 7.
    Bolen, P. L., Roth, K. A., and Freer, S. N. (1986),Appl. Environ. Microbiol. 52, 660–664.Google Scholar
  8. 8.
    Ho, N. W. Y., Lin, F. P., Huang, S., Andrews, P. C., and Tsao, G. T. (1990),Enzyme Microb. Technol. 12, 33–39.CrossRefGoogle Scholar
  9. 9.
    Verduyn, C., Van Kleef, R., Frank, J., Schreuder, H., Van Dijken, J. P., and Scheffers, W. A. (1985),Biochem. J. 226, 669–677.Google Scholar
  10. 10.
    Bruinenburg, P. M., de Bot, P. H. M., van Dijken, J. P., and Scheffers, W. A. (1984),Appl. Microbiol. Biotechnol. 19, 256–260.Google Scholar
  11. 11.
    Kador, P. F., Robinson, W. G., and Kinoshita, J. H. (1985),Annu. Rev. Pharmacol. Toxicol. 25, 691–714.CrossRefGoogle Scholar
  12. 12.
    Das, B. and Srivastava, S. K. (1985),Arch. Biochem. Biophys. 238, 670–679.CrossRefGoogle Scholar
  13. 13.
    Murphy, D. G. and Davidson, W. S. (1985),Biochem. Pharmacol. 34, 2961–2965.CrossRefGoogle Scholar
  14. 14.
    Bicho, P. A., Runnals, P. L., Cunningham, J. D., and Lee, H. (1988),Appl. Environ. Microbiol. 54, 50–54.Google Scholar
  15. 15.
    Lee, H., James, A. P., Zahab, D. M., Mahmourides, G., Maleszka, R., and Schneider, H. (1986),Appl. Environ. Microbiol. 51, 1252–1258.Google Scholar
  16. 16.
    Bradford, M., (1976),Anal. Biochem. 72, 248–254.CrossRefGoogle Scholar
  17. 17.
    Engel, P. C. (1977),Enzyme Kinetics: the Steady-State Approach, Chapman Hall, London.Google Scholar
  18. 18.
    Rizzi, M., Erlemann, P., Bui-Thanh, N., and Dellweg, H. (1988),Appl. Microbiol. Biotechnol. 29, 148–154.CrossRefGoogle Scholar
  19. 19.
    Varma, S. D. and Kinoshita, J. H. (1976),Biochem. Pharmacol. 25, 2505–2513.CrossRefGoogle Scholar
  20. 20.
    Nakai, N., Fujii, Y., Kobashi, K., and Nomura, K. (1985),Arch. Biochem. Biophys. 239, 491–496.CrossRefGoogle Scholar
  21. 21.
    Nazarova, G. N., Muzafarov, E. N., and Lyubimov, V. Yu. (1989),Biochemistry 54, Part 2: 680–684.Google Scholar
  22. 22.
    Bhatnagar, A., Liu, S., Das, B., Ansari, N. H., and Srivastava, S. K. (1990),Biochem. Pharmacol. 39, 1115–1124.CrossRefGoogle Scholar
  23. 23.
    Terubayashi, H., Sato, S., Nishimura, C., Kador, P. F., and Kinoshita, J. H. (1989),Kidney Int. 36, 843–851.CrossRefGoogle Scholar
  24. 24.
    Bhatnagar, A., Lui, S., Das, B. and Srivastava, S. K. (1989),Mol. Pharmacol. 36, 825–830.Google Scholar
  25. 25.
    Frohlich, D. R., Burris, T. E., and Brindley, W. A. (1989),Comp. Biochem. Physiol. 94B, 661–665.Google Scholar
  26. 26.
    Bohren, K. M., Bullock, B., Wermuth, B., and Gabbay, K. H. (1989),J. Biol. Chem. 264, 9547–9551.Google Scholar

Copyright information

© Humana Press Inc. 1991

Authors and Affiliations

  • Steven R. Webb
    • 1
  • Hung Lee
    • 1
  1. 1.Department of Environmental BiologyUniversity of GuelphGuelphCanada

Personalised recommendations