Encyclopedia of Malaria

Living Edition
| Editors: Peter G. Kremsner, Sanjeev Krishna

Pentose Phosphate Pathway

  • Paolo Arese
  • Valentina Gallo
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-8757-9_5-1



The pentose phosphate pathway (PPP) active in the host red blood cell and in the malaria parasite is complementary and alternative to glycolysis. PPP is the main producer of NADPH and pentose phosphates. NADPH regenerates reduced glutathione and reduced thioredoxin that protect hemoglobin and essential thiol groups from oxidation. Pentose phosphates are utilized for nucleoside, DNA, and RNA synthesis. The first, NADPH-producing reaction of PPP is catalyzed by glucose-6-phosphate dehydrogenase (G6PD). Mutations leading to G6PD deficiency are very frequent in malaric or ex-malaric regions, due to its protection against malaria. The parasite G6PD is very different from the human enzyme and as such a promising drug target candidate.

Overview of...


Pentose Phosphate Pathway Severe Malaria Cerebral Malaria G6PD Deficiency G6PD Activity 
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.
This is a preview of subscription content, log in to check access.


  1. Akide-Ndunge OB, Ayi K, Arese P. The Haldane malaria hypothesis: facts, artifacts, and a prophecy. Redox Rep. 2003;8(5):311–6. Review.CrossRefPubMedGoogle Scholar
  2. Arese P, De Flora A. Pathophysiology of hemolysis in glucose-6-phosphate dehydrogenase deficiency. Semin Hematol. 1990;27(1):1–40. Review.PubMedGoogle Scholar
  3. Arese P, Turrini F, Schwarzer E. Band 3/complement-mediated recognition and removal of normally senescent and pathological human erythrocytes. Cell Physiol Biochem. 2005;16:133–46. Review.CrossRefPubMedGoogle Scholar
  4. Arese P, Gallo V, Pantaleo A, Turrini F. Life and death of glucose-6-phosphate dehydrogenase (G6PD) deficient erythrocytes: role of redox stress and band 3 modifications. Transfus Med Hemother. 2012;39(5):328–34. Review.PubMedCentralCrossRefPubMedGoogle Scholar
  5. Atamna H, Pascarmona G, Ginsburg H. Hexose-monophosphate shunt activity in intact Plasmodium falciparum-infected erythrocytes and in free parasites. Mol Biochem Parasitol. 1994;67(1):79–89.CrossRefPubMedGoogle Scholar
  6. Ayi K, Cappadoro M, Branca M, Turrini F, Arese P. Plasmodium falciparum glutathione metabolism and growth are independent of glutathione system of host erythrocyte. FEBS Lett. 1998;424(3):257–61.CrossRefPubMedGoogle Scholar
  7. Barrett MP. The pentose phosphate pathway and parasitic protozoa. Parasitol Today. 1997;13(1):11–6. Review.CrossRefPubMedGoogle Scholar
  8. Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th ed. New York: Freeman; 2001.Google Scholar
  9. Bienzle U, Ayeni O, Lucas AO, Luzzatto L. Glucose-6-phosphate dehydrogenase and malaria. Greater resistance of females heterozygous for enzyme deficiency and of males with non-deficient variant. Lancet. 1972;1(7742):107–10.CrossRefPubMedGoogle Scholar
  10. Bozdech Z, Ginsburg H. Data mining of the transcriptome of Plasmodium falciparum: the pentose phosphate pathway and ancillary processes. Malar J. 2005;4(1):e17.CrossRefGoogle Scholar
  11. Cappadoro M, Giribaldi G, O’Brien E, Turrini F, Mannu F, Ulliers D, et al. Early phagocytosis of glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes parasitized by Plasmodium falciparum may explain malaria protection in G6PD deficiency. Blood. 1998;92(7):2527–34.PubMedGoogle Scholar
  12. Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008;371:64–74. Review.CrossRefPubMedGoogle Scholar
  13. Gaetani GD, Parker JC, Kirkman HN. Intracellular restraint: a new basis for the limitation in response to oxidative stress in human erythrocytes containing low-activity variants of glucose-6-phosphate dehydrogenase. Proc Natl Acad Sci U S A. 1974;71:3584–7.PubMedCentralCrossRefPubMedGoogle Scholar
  14. Ginsburg H, Atamna H, Shalmiev G, Kanaani J, Krugliak M. Resistance of glucose-6-phosphate dehydrogenase deficiency to malaria: effects of fava bean hydroxypyrimidine glucosides on Plasmodium falciparum growth in culture and on the phagocytosis of infected cells. Parasitology. 1996;113:7–18.CrossRefPubMedGoogle Scholar
  15. Greene LS. G6PD deficiency as protection against falciparum malaria: an epidemiologic critique of population and experimental studies. Yearb Phys Anthropol. 1993;36:153–78. Review.CrossRefGoogle Scholar
  16. Guindo A, Fairhurst RM, Doumbo OK, Wellems TE, Diallo DA. X-linked G6PD deficiency protects hemizygous males but not heterozygous females against severe malaria. PLoS Med. 2007;4(3):e66.PubMedCentralCrossRefPubMedGoogle Scholar
  17. Hempelmann E, Wilson RJ. Detection of glucose-6-phosphate dehydrogenase in malarial parasites. Mol Biochem Parasitol. 1981;2(3–4):197–204.CrossRefPubMedGoogle Scholar
  18. Jortzik E, Mailu BM, Preuss J, Fischer M, Bode L, Rahlfs S, et al. Glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase: a unique bifunctional enzyme from Plasmodium falciparum. Biochem J. 2011;436(3):641–50.CrossRefPubMedGoogle Scholar
  19. Joshi S, Singh AR, Kumar A, Misra PC, Siddiqi MI, Saxena JK. Molecular cloning and characterization of Plasmodium falciparum transketolase. Mol Biochem Parasitol. 2008;160(1):32–41.CrossRefPubMedGoogle Scholar
  20. Kirkman HN, Gaetani GF. Regulation of glucose-6-phosphate dehydrogenase in human erythrocytes. J Biol Chem. 1986;261:4033–8.PubMedGoogle Scholar
  21. Kurdi-Haidar B, Luzzatto L. Expression and characterization of glucose-6-phosphate dehydrogenase of Plasmodium falciparum. Mol Biochem Parasitol. 1990;41(1):83–91.CrossRefPubMedGoogle Scholar
  22. Ling IT, Wilson RJ. Glucose-6-phosphate dehydrogenase activity of the malaria parasite Plasmodium falciparum. Mol Biochem Parasitol. 1988;31(1):47–56.CrossRefPubMedGoogle Scholar
  23. López C, Saravia C, Gomez A, Hoebeke J, Patarroyo MA. Mechanisms of genetically-based resistance to malaria. Gene. 2010;467(1–2):1–12. Review.CrossRefPubMedGoogle Scholar
  24. Luzzatto L, Usanga E, Reddy S. Glucose-6-phosphate dehydrogenase deficient red cells: resistance of infection by malaria parasites. Science. 1969;164:839–41.CrossRefPubMedGoogle Scholar
  25. Luzzatto L, Mehta A, Vuillamy T. Glucose 6-phosphate dehydrogenase deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill; 2001. p. 4517–53.Google Scholar
  26. Manganelli G, Masullo U, Passarelli S, Filosa S. Glucose-6-phosphate dehydrogenase deficiency: disadvantages and possible benefits. Cardiovasc Hematol Disord Drug Targets. 2013;13(1):73–82.CrossRefPubMedGoogle Scholar
  27. Mason PJ, Bautista JM, Gilsanz F. G6PD deficiency: the genotype-phenotype association. Blood Rev. 2007;21:267–83.CrossRefPubMedGoogle Scholar
  28. Minucci A, Moradkhani K, Hwang MJ, Zuppi C, Giardina B, Capoluongo E. Glucose-6-phosphate dehydrogenase (G6PD) mutations database: review of the “old” and update of the new mutations. Blood Cells Mol Dis. 2012;48(3):154.CrossRefPubMedGoogle Scholar
  29. Nkhoma ET, Poole C, Vannappagari V, Hall SA, Beutler E. The global prevalence of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis. Blood Cells Mol Dis. 2009;42:267–78. Review.CrossRefPubMedGoogle Scholar
  30. Notaro R, Afolayan A, Luzzatto L. Human mutations in glucose 6-phosphate dehydrogenase reflect evolutionary history. FASEB J. 2000;14(3):485–94.PubMedGoogle Scholar
  31. O’Brien E, Kurdi-Haidar B, Wanachiwanawin W, Carvajal JL, Vulliamy TJ, Cappadoro M, et al. Cloning of the glucose 6-phosphate dehydrogenase gene from Plasmodium falciparum. Mol Biochem Parasitol. 1994;64(2):313–26.CrossRefPubMedGoogle Scholar
  32. Perl A. The pathogenesis of transaldolase deficiency. IUBMB Life. 2007;59(6):365–73. Review.CrossRefPubMedGoogle Scholar
  33. Perl A, Hanczko R, Telarico T, Oaks Z, Landas S. Oxidative stress, inflammation and carcinogenesis are controlled through the pentose phosphate pathway by transaldolase. Trends Mol Med. 2011;17(7):395–403. Review.PubMedCentralCrossRefPubMedGoogle Scholar
  34. Persico MG, Viglietto G, Martini G, Toniolo D, Paonessa G, Moscatelli C, et al. Isolation of human glucose-6-phosphate dehydrogenase (G6PD) cDNA clones: primary structure of the protein and unusual 5′ non-coding region. Nucleic Acids Res. 1986;14(6):2511–22.PubMedCentralCrossRefPubMedGoogle Scholar
  35. Preuss J, Jortzik E, Becker K. Glucose-6-phosphate metabolism in Plasmodium falciparum. IUBMB Life. 2012a;64(7):603–11. Review.CrossRefPubMedGoogle Scholar
  36. Preuss J, Hedrick M, Sergienko E, Pinkerton A, Mangravita-Novo A, Smith L, et al. High-throughput screening for small-molecule inhibitors of Plasmodium falciparum glucose-6-phosphate dehydrogenase 6-phosphogluconolactonase. J Biomol Screen. 2012b;17(6):738–51.CrossRefPubMedGoogle Scholar
  37. Roth Jr EF, Raventos-Suarez C, Perkins M, Nagel RL. Glutathione stability and oxidative stress in P. falciparum infection in vitro: responses of normal and G6PD deficient cells. Biochem Biophys Res Commun. 1982;109(2):355–62.CrossRefPubMedGoogle Scholar
  38. Ruwende C, Khoo SC, Snow RW, Yates SN, Kwiatkowski D, Gupta S, et al. Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Nature. 1995;376:246–9.CrossRefPubMedGoogle Scholar
  39. Samland AK, Sprenger GA. Transaldolase: from biochemistry to human disease. Int J Biochem Cell Biol. 2009;41(7):1482–94.CrossRefPubMedGoogle Scholar
  40. Schwarzer E, Kuehn H, Arese P. The hidden faces of hemozoin and its dangerous midwives. Trends Parasitol. 2003;19(5):197–8.CrossRefPubMedGoogle Scholar
  41. Stanton RC. Glucose-6-phosphate dehydrogenase, NADPH, and cell survival. IUBMB Life. 2012;64(5):362–9. Review.PubMedCentralCrossRefPubMedGoogle Scholar
  42. Takizawa T, Huang IY, Ikuta T, Yoshida A. Human glucose-6-phosphate dehydrogenase: primary structure and cDNA cloning. Proc Natl Acad Sci U S A. 1986;83(12):4157–61.PubMedCentralCrossRefPubMedGoogle Scholar
  43. Wamelink MM, Struys EA, Jakobs C. The biochemistry, metabolism and inherited defects of the pentose phosphate pathway: a review. J Inherit Metab Dis. 2008;31(6):703–17.CrossRefPubMedGoogle Scholar
  44. Wood T. Physiological functions of the pentose phosphate pathway. Cell Biochem Funct. 1986;4:241–7. Review.CrossRefPubMedGoogle Scholar
  45. Yoshida A. Hemolytic anemia and G6PD deficiency. Science. 1973;179:532–7.CrossRefPubMedGoogle Scholar
  46. Yoshida A, Roth EF. Glucose-6-phosphate dehydrogenase of malaria parasite Plasmodium falciparum. Blood. 1987;69:1528–30.PubMedGoogle Scholar
  47. Zhao J, Zhong CJ. A review on research progress of transketolase. Neurosci Bull. 2009;25(2):94–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of OncologyUniversity of TorinoTorinoItaly