Table of Contents
Molecular Biology International
Volume 2011 (2011), Article ID 135701, 10 pages
http://dx.doi.org/10.4061/2011/135701
Review Article

Glucose-6-Phosphate Dehydrogenase of Trypanosomatids: Characterization, Target Validation, and Drug Discovery

1Research Unit for Tropical Diseases, de Duve Institute, TROP 74.39, Avenue Hippocrate 74, 1200 Brussels, Belgium
2Department of Chemistry, Heritage Institute of Technology, Chowbaga Road, Anandapur, Kolkata 700107, India
3Laboratory of Experimental Medicine, Université Libre de Bruxelles, Route de Lennik 808, CP 618, 1070 Brussels, Belgium
4Laboratory of Biochemistry, Université Catholique de Louvain, Brussels, Belgium
5Laboratório Nacional de Biociências (LNBio), Centro Nacional de Pesquisas em Energia e Materiais (CNPEM), Caixa Postal 6192, 13083-970 Campinas, SP, Brazil

Received 9 December 2010; Accepted 20 January 2011

Academic Editor: Hemanta K. Majumder

Copyright © 2011 Shreedhara Gupta et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. P. Barrett, R. J. S. Burchmore, A. Stich et al., “The trypanosomiases,” The Lancet, vol. 362, no. 9394, pp. 1469–1480, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. S. H. Funayama, S. Funayama, I. Y. Ito, and L. A. Veiga, “Trypanosoma cruzi: kinetic properties of glucose-6-phosphate dehydrogenase,” Experimental Parasitology, vol. 43, no. 2, pp. 376–381, 1977. View at Google Scholar · View at Scopus
  3. D. Barry, R. McCulloch, J. Mottram, and A. Acosta-Serrano, Trypanosomes: After the Genome, Horizon Bioscience, Norfolk, UK, 2007.
  4. A. Prata, “Clinical and epidemiological aspects of Chagas disease,” Lancet Infectious Diseases, vol. 1, no. 2, pp. 92–100, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. K. M. Tyler and D. M. Engman, “The life cycle of Trypanosoma cruzi revisited,” International Journal for Parasitology, vol. 31, no. 5-6, pp. 472–481, 2001. View at Publisher · View at Google Scholar · View at Scopus
  6. B. A. Burleigh and A. M. Woolsey, “Cell signalling and Trypanosoma cruzi invasion,” Cellular Microbiology, vol. 4, no. 11, pp. 701–711, 2002. View at Publisher · View at Google Scholar · View at Scopus
  7. P. J. Myler and N. Fasel, Leishmania: After the Genome, Caister Academic Press, Norfolk, UK, 2008.
  8. J. C. Dujardin, D. González-Pacanowska, S. L. Croft, O. F. Olesen, and G. F. Späth, “Collaborative actions in anti-trypanosomatid chemotherapy with partners from disease endemic areas,” Trends in Parasitology, vol. 26, pp. 395–403, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  9. S. Nwaka and A. Hudson, “Innovative lead discovery strategies for tropical diseases,” Nature Reviews Drug Discovery, vol. 5, no. 11, pp. 941–955, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. V. Delespaux and H. P. de Koning, “Drugs and drug resistance in African trypanosomiasis,” Drug Resistance Updates, vol. 10, no. 1-2, pp. 30–50, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. C. L. M. J. Verlinde, V. Hannaert, C. Blonski et al., “Glycolysis as a target for the design of new anti-trypanosome drugs,” Drug Resistance Updates, vol. 4, no. 1, pp. 50–65, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  12. T. K. Smith and P. Bütikofer, “Lipid metabolism in Trypanosoma brucei,” Molecular and Biochemical Parasitology, vol. 172, no. 2, pp. 66–79, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. N. Galland and P. A. M. Michels, “Comparison of the peroxisomal matrix protein import system of different organisms. Exploration of possibilities for developing inhibitors of the import system of trypanosomatids for anti-parasite chemotherapy,” European Journal of Cell Biology, vol. 89, pp. 621–637, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. F. Agüero, B. Al-Lazikani, M. Aslett et al., “Genomic-scale prioritization of drug targets: the TDR Targets database,” Nature Reviews Drug Discovery, vol. 7, no. 11, pp. 900–907, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. G. J. Crowther, D. Shanmugam, S. J. Carmona et al., “Identification of attractive drug targets in neglected- disease pathogens using an in silico approach,” PLoS Neglected Tropical Diseases, vol. 4, no. 8, article e804, 2010. View at Publisher · View at Google Scholar · View at PubMed
  16. M. P. Barrett, “The pentose phosphate pathway and parasitic protozoa,” Parasitology Today, vol. 13, no. 1, pp. 11–16, 1997. View at Publisher · View at Google Scholar · View at Scopus
  17. N. J. Kruger and A. Von Schaewen, “The oxidative pentose phosphate pathway: structure and organisation,” Current Opinion in Plant Biology, vol. 6, no. 3, pp. 236–246, 2003. View at Publisher · View at Google Scholar · View at Scopus
  18. M. A. Rosemeyer, “The biochemistry of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and glutathione reductase,” Cell Biochemistry and Function, vol. 5, no. 2, pp. 79–95, 1987. View at Google Scholar · View at Scopus
  19. T. Wood, “Physiological functions of the pentose phosphate pathway,” Cell Biochemistry and Function, vol. 4, no. 4, pp. 241–247, 1986. View at Google Scholar · View at Scopus
  20. G. Ronquist and E. Theodorsson, “Inherited, non-spherocytic haemolysis due to deficiency of glucose-6-phosphate dehydrogenase,” Scandinavian Journal of Clinical and Laboratory Investigation, vol. 67, no. 1, pp. 105–111, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  21. MD. Cappellini and G. Fiorelli, “Glucose-6-phosphate dehydrogenase deficiency,” The Lancet, vol. 371, no. 9606, pp. 64–74, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. I. Raw, “Some aspects of carbohydrate metabolism of cultural forms of Trypanosoma cruzi,” Revista do Instituto de Medicina Tropical de São Paulo, vol. 1, pp. 192–194, 1959. View at Google Scholar
  23. J. F. Ryley, “Studies on the metabolism of the protozoa. 9. Comparative metabolism of blood-stream and culture forms of Trypanosoma rhodesiense,” The Biochemical Journal, vol. 85, pp. 211–223, 1962. View at Google Scholar · View at Scopus
  24. R. Mancilla and C. Naquira, “Comparative metabolism of C14-glucose in two strains of Trypanosoma cruzi,” The Journal of protozoology, vol. 11, pp. 509–513, 1964. View at Google Scholar
  25. R. Mancilla, C. Náquira, and C. Lanas, “Metabolism of glucose labelled with carbon—14 in Leishmania enriettii,” Nature, vol. 206, no. 4979, pp. 27–28, 1965. View at Publisher · View at Google Scholar · View at Scopus
  26. R. Mancilla, C. Naquira, and C. Lanas, “Metabolism of glucose-C in Leishmania brasiliensis,” Comparative Biochemistry and Physiology, vol. 28, no. 1, pp. 227–232, 1969. View at Google Scholar · View at Scopus
  27. C. N. Cronín, D. P. Nolan, and H. P. Voorheis, “The enzymes of the classical pentose phosphate pathway display differential activities in procyclic and bloodstream forms of Trypanosoma brucei,” FEBS Letters, vol. 244, no. 1, pp. 26–30, 1989. View at Publisher · View at Google Scholar · View at Scopus
  28. N. Heise and F. R. Opperdoes, “Purification, localisation and characterisation of glucose-6-phosphate dehydrogenase of Trypanosoma brucei,” Molecular and Biochemical Parasitology, vol. 99, no. 1, pp. 21–32, 1999. View at Publisher · View at Google Scholar · View at Scopus
  29. F. Duffieux, J. Van Roy, P. A. M. Michels, and F. R. Opperdoes, “Molecular characterization of the first two enzymes of the pentose-phosphate pathway of Trypanosoma brucei: glucose-6-phosphate dehydrogenase and 6-phosphogluconolactonase,” Journal of Biological Chemistry, vol. 275, no. 36, pp. 27559–27565, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. F. R. Opperdoes and P. Borst, “Localization of non glycolytic enzymes in a microbody like organelle in Trypanosoma brucei: the glycosome,” FEBS Letters, vol. 80, no. 2, pp. 360–364, 1977. View at Publisher · View at Google Scholar · View at Scopus
  31. C. Colasante, M. Ellis, T. Ruppert, and F. Voncken, “Comparative proteomics of glycosomes from bloodstream form and procyclic culture form Trypanosoma brucei brucei,” Proteomics, vol. 6, no. 11, pp. 3275–3293, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. D. Vertommen, J. Van Roy, J. P. Szikora, M. H. Rider, P. A. M. Michels, and F. R. Opperdoes, “Differential expression of glycosomal and mitochondrial proteins in the two major life-cycle stages of Trypanosoma brucei,” Molecular and Biochemical Parasitology, vol. 158, no. 2, pp. 189–201, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. P. A. M. Michels, F. Bringaud, M. Herman, and V. Hannaert, “Metabolic functions of glycosomes in trypanosomatids,” Biochimica et Biophysica Acta, vol. 1763, no. 12, pp. 1463–1477, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  34. O. Misset, O. J. M. Bos, and F. R. Opperdoes, “Glycolytic enzymes of Trypanosoma brucei. Simultaneous purification, intraglycosomal concentrations and physical properties,” European Journal of Biochemistry, vol. 157, no. 2, pp. 441–453, 1986. View at Google Scholar · View at Scopus
  35. F. R. Opperdoes, “Compartmentation of carbohydrate metabolism in trypanosomes,” Annual Review of Microbiology, vol. 41, pp. 127–151, 1987. View at Google Scholar · View at Scopus
  36. D. A. Maugeri and J. J. Cazzulo, “The pentose phosphate pathway in Trypanosoma cruzi,” FEMS Microbiology Letters, vol. 234, no. 1, pp. 117–123, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. D. A. Maugeri, J. J. Cazzulo, R. J. S. Burchmore, M. P. Barrett, and P. O. J. Ogbunude, “Pentose phosphate metabolism in Leishmania mexicana,” Molecular and Biochemical Parasitology, vol. 130, no. 2, pp. 117–125, 2003. View at Publisher · View at Google Scholar · View at Scopus
  38. N. J. Veitch, D. A. Maugeri, J. J. Cazzulo, Y. Lindqvist, and M. P. Barrett, “Transketolase from Leishmania mexicana has a dual subcellular localization,” Biochemical Journal, vol. 382, no. 2, pp. 759–767, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  39. F. R. Opperdoes and J. P. Szikora, “In silico prediction of the glycosomal enzymes of Leishmania major and trypanosomes,” Molecular and Biochemical Parasitology, vol. 147, no. 2, pp. 193–206, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  40. . Funayama Sh., S. Funayama, I. Y. Ito, and L. A. Veiga, “Trypanosoma cruzi: kinetic properties of glucose-6-phosphate dehydrogenase,” Experimental Parasitology, vol. 43, no. 2, pp. 376–381, 1977. View at Google Scholar · View at Scopus
  41. J. A. Lupiañez, F. J. Adroher, A. M. Vargas, and A. Osuna, “Differential behaviour of glucose 6-phosphate dehydrogenase in two morphological forms of Trypanosoma cruzi,” International Journal of Biochemistry, vol. 19, no. 11, pp. 1085–1089, 1987. View at Google Scholar · View at Scopus
  42. V. Hannaert, E. Saavedra, F. Duffieux et al., “Plant-like traits associated with metabolism of Trypanosoma parasites,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 3, pp. 1067–1071, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  43. M. Igoillo-Esteve and J. J. Cazzulo, “The glucose-6-phosphate dehydrogenase from Trypanosoma cruzi: its role in the defense of the parasite against oxidative stress,” Molecular and Biochemical Parasitology, vol. 149, no. 2, pp. 170–181, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  44. M. Igoillo-Esteve, D. Maugeri, A. L. Stern, P. Beluardi, and J. J. Cazzulo, “The pentose phosphate pathway in Trypanosoma cruzi: a potential target for the chemotherapy of Chagas disease,” Anais da Academia Brasileira de Ciencias, vol. 79, no. 4, pp. 649–663, 2007. View at Google Scholar · View at Scopus
  45. A. T. Cordeiro, O. H. Thiemann, and P. A. M. Michels, “Inhibition of Trypanosoma brucei glucose-6-phosphate dehydrogenase by human steroids and their effects on the viability of cultured parasites,” Bioorganic and Medicinal Chemistry, vol. 17, no. 6, pp. 2483–2489, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  46. A. T. Cordeiro and O. H. Thiemann, “16-Bromoepiandrosterone, an activator of the mammalian immune system, inhibits glucose 6-phosphate dehydrogenase from Trypanosoma cruzi and is toxic to these parasites grown in culture,” Bioorganic and Medicinal Chemistry, vol. 18, no. 13, pp. 4762–4768, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  47. I. Wenderoth, R. Scheibe, and A. Von Schaewen, “Identification of the cysteine residues involved in redox modification of plant plastidic glucose-6-phosphate dehydrogenase,” Journal of Biological Chemistry, vol. 272, no. 43, pp. 26985–26990, 1997. View at Publisher · View at Google Scholar · View at Scopus
  48. C. Cséke, A. Balogh, and G. L. Farkas, “Redox modulation of glucose-6-P dehydrogenase in Anacystis nidulans and its ‘uncoupling’ by phage infection,” FEBS Letters, vol. 126, no. 1, pp. 85–88, 1981. View at Google Scholar · View at Scopus
  49. A. E. Leroux, D. A. Maugeri, F. R. Opperdoes, J. J. Cazzulo, and C. Nowicki, “Comparative studies on the biochemical properties of the malic enzymes from Trypanosoma cruzi and Trypanosoma brucei,” FEMS Microbiology Letters, vol. 314, no. 1, pp. 25–33, 2011. View at Publisher · View at Google Scholar · View at PubMed
  50. P. Marks and J. Banks, “Inhibition of mammalian glucose-6-phosphate dehydrogenase by steroids,” Proceedings of the National Academy of Sciences of the United States of America, vol. 46, pp. 447–452, 1960. View at Google Scholar
  51. G. Gordon, M. C. Mackow, and H. R. Levy, “On the mechanism of interaction of steroids with human glucose 6-phosphate dehydrogenase,” Archives of Biochemistry and Biophysics, vol. 318, no. 1, pp. 25–29, 1995. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  52. K. R. Rasmussen, M. J. Arrowood, and M. C. Healey, “Effectiveness of dehydroepiandrosterone in reduction of cryptosporidial activity in immunosuppressed rats,” Antimicrobial Agents and Chemotherapy, vol. 36, no. 1, pp. 220–222, 1992. View at Google Scholar · View at Scopus
  53. D. Freilich, S. Ferris, M. Wallace et al., “16α-bromoepiandrosterone, a dehydroepiandrosterone (DHEA) analogue, inhibits Plasmodium falciparum and Plasmodium berghei growth,” American Journal of Tropical Medicine and Hygiene, vol. 63, no. 5-6, pp. 280–283, 2000. View at Google Scholar · View at Scopus
  54. J. Morales-Montor, S. Baig, R. Mitchell, K. Deway, C. Hallal-Calleros, and R. T. Damian, “Immunoendocrine interactions during chronic cysticercosis determine male mouse feminization: role of IL-6,” Journal of Immunology, vol. 167, no. 8, pp. 4527–4533, 2001. View at Google Scholar · View at Scopus
  55. C. D. Dos Santos, M. P. Alonso Toldo, and J. C. Do Prado, “Trypanosoma cruzi: the effects of dehydroepiandrosterone (DHEA) treatment during experimental infection,” Acta Tropica, vol. 95, no. 2, pp. 109–115, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  56. J. C. Carrero, C. Cervantes, N. Moreno-Mendoza, E. Saavedra, J. Morales-Montor, and J. P. Laclette, “Dehydroepiandrosterone decreases while cortisol increases in vitro growth and viability of Entamoeba histolytica,” Microbes and Infection, vol. 8, no. 2, pp. 323–331, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  57. J. A. Vargas-Villavicencio, C. Larralde, and J. Morales-Montor, “Treatment with dehydroepiandrosterone in vivo and in vitro inhibits reproduction, growth and viability of Taenia crassiceps metacestodes,” International Journal for Parasitology, vol. 38, no. 7, pp. 775–781, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. K. P. Luna, I. P. Hernández, C. M. Rueda, M. M. Zorro, S. L. Croft, and P. Escobar, “In vitro susceptibility of Trypanosoma cruzi strains from Santander, Colombia, to hexadecylphosphocholine (miltefosine), nifurtimox and benznidazole,” Biomedica, vol. 29, no. 3, pp. 448–455, 2009. View at Google Scholar
  59. S. Gupta, A. T. Cordeiro, and P. A. M. Michels, “Glucose-6-phosphate dehydrogenase is the target for the trypanocidal action of human steroids,” Molecular and Biochemical Parasitology, vol. 176, no. 2, pp. 112–115, 2011. View at Publisher · View at Google Scholar · View at PubMed
  60. A. Cornish-Bowden, “Why is uncompetitive inhibition so rare? A possible explanation, with implications for the design of drugs and pesticides,” FEBS Letters, vol. 203, no. 1, pp. 3–6, 1986. View at Google Scholar · View at Scopus