Advertisement

The Role of Glutathionylspermidine and Trypanothione in Regulation of Intracellular Spermidine Levels During Growth of Crithidia Fasciculata

  • Alan H. Fairlamb
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 250)

Abstract

Trypanosomatids are unusual in that a considerable proportion of their intracellular spermidine and glutathione (GSH) is found as the conjugate Ni-glutathionylspermidine (GSH-SPD) and N1-, N8-bis-(glutathionyl)spermidine (T[SH]2)1. The latter compound is unique to the parasitic and free-living Trypanosomatidae and has been assigned the trivial name trypano-thione2.

Keywords

Glutathione Reductase Ornithine Decarboxylase Stationary Phase Cell Bloodstream Form Buthionine Sulfoximine 
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.
    Fairlamb, A. H., Henderson, G. B., and Cerami, A., 1986, The biosynthesis of trypanothione and N1-glutathionylspermidine in Crithidia fasciculateata, Mol. Biochem. Parasitol., 21: 247–257PubMedCrossRefGoogle Scholar
  2. 2.
    Fairlamb, A. H., Blackburn, P., Ulrich, P., Chait, B. T., and Cerami, A., 1985, Trypanothione: A novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids, Science, 227: 1485–1487.PubMedCrossRefGoogle Scholar
  3. 3.
    Fairlamb, A. H., and Cerami, A., 1985, Identification of a novel, thiol-containing co-factor essential for glutathione reductase enzyme activity in trypanosomtids, Mol. Biochem. Parasitol., 14: 187–198.PubMedCrossRefGoogle Scholar
  4. 4.
    Henderson, G. B., Fairlamb, A. H., and Cerami, A., 1987, Trypanothione dependent peroxide metabolism in Crithidia fasciculata and Trypanosoma bruceji, Mol. Biochem. Parasitol., 24: 39–45.PubMedCrossRefGoogle Scholar
  5. 5.
    Fairlamb, A. H., and Henderson, G. B., 1987, Metabolism of trypanothione and glutathionylspermidine in trypanosomatids, in: “Host-Parasite Molecular Recognition and Interaction in Protozoal Infections,” K.-P. Chang and D. Snary, eds., pp. 29–40, NATO-ASI Series, Heidelberg.CrossRefGoogle Scholar
  6. 6.
    Shames, S. L., Fairlamb, A. H., Cerami, A., and Walsh, C. T., 1986, Purification and characterization of trypanothione reductase from Crithidia fasciculate, a newly discovered member of the family of disulfide-containing flavoprotein reductases, Biochemistry, 25: 3519–3526.PubMedCrossRefGoogle Scholar
  7. 7.
    Krauth-Siegel, R. L., Enders, B., Henderson, G. B., Fairlamb, A. H., and Schirmer, R. H., 1987, Trypanothione reductase from Trypanosoma cruzi: Purification and characterization of the crystalline enzyme, Eur. J. Biochem., 164: 123–128.PubMedCrossRefGoogle Scholar
  8. 8.
    Henderson, G. B., Fairlamb, A. H., Ulrich, P., and Cerami, A., 1987, Substrate specificity of the flavoprotein trypanothione disulphide reductase from Crithidia fasciculata, Biochemistry, 26: 3023–3027.PubMedCrossRefGoogle Scholar
  9. 9.
    Docampo, R., and Moreno, S. N. J., 1986, Free radical metabolism of antiparasitic agents, Fed. Proc., 45: 2471–2476.PubMedGoogle Scholar
  10. 10.
    Le Trang, N., Meshnick, S. R., Kitchener, K., Eaton, J. W., and Cerami, A., 1983, Iron-containing Superoxide dismutase from Crithidia fasciculata, J. Biol. Chem., 258: 125–130.Google Scholar
  11. 11.
    Henderson, G.B., Ulrich, P.U., Fairlamb, A.H., Rosenberg, I., Pereira, M., Sela, M. and Cerami, A. (1988) “Subversive substrates” for the enzyme trypanothione disulfide reductase: A new approach to chemotherapy of Chagas’ disease. Proc. Natl. Acad. Sei., USA, in press.Google Scholar
  12. 12.
    Bacchi, C.J., Nathan, H.C. and Hutner, S.H., 1980, Polyamine metabolism: A potential therapeutic target in trypanosomes, Science, 210: 332–334.PubMedCrossRefGoogle Scholar
  13. 13.
    Fairlamb, A.H., Henderson, G.B., Bacchi, C.J., and Cerami, A., 1987, In vivo effects of difluoromethylornithine on trypanothione and polyamine levels in bloodstream forms of Trypanosoma brucei, Mol. Biochem. Parasitol., 24: 185–191.PubMedCrossRefGoogle Scholar
  14. 14.
    Bellofatto, V., Fairlamb, A.H., Henderson, G.B., and Cross, G.A.M., 1987, Biochemical changes associated with alpha-difluoromethylornithine uptake and resistance in Trypanosoma brucei, Mol. Biochem. Parasitol., 25: 227–238.PubMedCrossRefGoogle Scholar
  15. 15.
    Griffith, O.W. and Meister, A., 1979, Potent and specific inhibition of glutathione synthesis by buthionine sulphoximine (S-n-butyl homocys-teine sulphoximine), J.Biol.Chem., 254: 7558–7560.PubMedGoogle Scholar
  16. 16.
    Arrick, B.A., Griffith, O.W. and Cerami, A., 1981, Inhibition of glutathione synthesis as a chemotherapeutic strategy for trypanoso-miasis, J. Exp. Med., 153: 720–725.PubMedCrossRefGoogle Scholar
  17. 17.
    Bitonti, A.J., Dumont, J.A. and McCann, P.P., 1986, Characterization of Trypanosoma brucei brucei S-adenosyl-L-methionine decarboxylase and its inhibition by Berenil, pentamidine and methylglyoxal bis(guanyl-hydrazone), Biochem. J., 237: 685–689.PubMedGoogle Scholar
  18. 18.
    Fairlamb, A.H., Henderson, G.B. and Cerami, A., 1988, Complex-formation of dihydrotrypanothione with the trivalent arsenical drug, melarsen oxide, and its effect as an inhibitor of trypanothione reductase in Trypanosoma brucei., submitted for publication.Google Scholar
  19. 19.
    McCann, P.P., Bacchi, C.J., Nathan, H.C. and Sjoerdsma, A., 1983, Difluoromethylornithine and the rational development of polyamine antagonists for the cure of protozoan infections in: “Mechanisms of Drug Action,” Singer, T.P. and Ondarza, R.N., eds., Academic Press, New York.Google Scholar
  20. 20.
    Tabor, H., and Tabor, C. E., 1975, Isolation, characterization, and turnover of glutathionylspermidine from Escherichia coli, J. Biol. Chem., 250: 2648–2654.PubMedGoogle Scholar
  21. 21.
    Tabor, C.E. and Tabor, H., 1970, The complete conversion of spermidine to a peptide derivative in Escherichia coli. Biochem. Biophys. Res. Comm., 41: 232–238.PubMedCrossRefGoogle Scholar
  22. 22.
    Shim, H., and Fairlamb, A. H., 1988, Levels of polyamines, glutathione and glutathione-spermidine conjugates during growth of the insect trypanosomatid Crithidia fasciculata, J. Gen. Microbiol., 134: 807–817.PubMedGoogle Scholar
  23. 23.
    Westhall, F. and Hesser, H., 1974, Fifteen-minute acid hydrolysis of peptides. Anal. Biochem., 61: 610–613.CrossRefGoogle Scholar
  24. 24.
    Keithly, J.S. and Fairlamb, A.H., 1988, Inhibition of Leishmania species by α-difluoromethylornithine in: “NATO-ASI Series: The First Centenary (1885–1985) New Strategies for Control,” Hart, D.T., ed., in press.Google Scholar
  25. 25.
    Phillips, M.A., Coffino, P. and Wang, C.C., 1988, Cloning and sequencing of the ornithine decarboxylase gene from Trypanosoma brucei: Implications for enzyme turnover and selective difluoromethylornithine inhibition, J.Biol.Chem., 262: 8721–8727Google Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Alan H. Fairlamb
    • 1
  1. 1.Department of Medical ProtozoologyLondon School of Hygiene and Tropical MedicineLondonUK

Personalised recommendations