Encyclopedia of Malaria

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

Hemoglobin Digestion

  • Daniel E. Goldberg
  • Philip J. Rosenthal
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-8757-9_7-1


Intraerythrocytic malaria parasites digest most of the hemoglobin of their host cells (Goldberg 2005; Rosenthal 2002). In a 70 kg person with a heavy Plasmodium falciparuminfection (20 % parasitemia), assuming 75 % degradation of hemoglobin within each infected erythrocyte, about one-third of a pound (~150 g) of hemoglobin is consumed in a single round of parasite growth. This, then, is an enormous catabolic effort. The purpose of hemoglobin degradation is not fully established. Parasites use some of the liberated amino acids for protein synthesis, and this utilization is increased when the exogenous amino acid supply is restricted. Indeed, cultures grown in the absence of most exogenous amino acids have near-normal proliferation (isoleucine supplementation is required, as human hemoglobin lacks this amino acid). In addition, a role for hemoglobin digestion in maintaining osmotic balance, perhaps even preventing premature rupture as the parasite grows, has been proposed....


Aspartic Protease Digestive Vacuole Vinyl Sulfone Fluoromethyl Ketone Hemoglobin Degradation 
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. Bakar NA, Klonis N, Hanssen E, Chan C, Tilley L. Digestive-vacuole genesis and endocytic processes in the early intraerythrocytic stages of Plasmodium falciparum. J Cell Sci. 2010;123:441–50.PubMedCrossRefGoogle Scholar
  2. Berry C, Goldberg DE. Food vacuole plasmepsins. In: Rawlings ND, Salvesen GS, editors. Handbook of proteolytic enzymes. Oxford: Academic; 2013. p. 98–103.CrossRefGoogle Scholar
  3. Bhaumik P, Gustchina A, Wlodawer A. Structural studies of vacuolar plasmepsins. Biochim Biophys Acta. 2012;1824:207–23.PubMedCentralPubMedCrossRefGoogle Scholar
  4. Chugh M, Sundararaman V, Kumar S, Reddy VS, Siddiqui WA, Stuart KD, Malhotra P. Protein complex directs hemoglobin to hemozoin formation in Plasmodium falciparum. Proc Natl Acad Sci U S A. 2013;110:5392–7.PubMedCentralPubMedCrossRefGoogle Scholar
  5. Ettari R, Bova F, Zappalà M, Grasso S, Micale N. Falcipain-2 inhibitors. Med Res Rev. 2010;30(1):136–67.PubMedGoogle Scholar
  6. Goldberg DE. Hemoglobin degradation. In: Sullivan DJ, Krishna S, editors. Current topics in microbiology and immunology. Antimalarial chemotherapy. Heidelberg: Springer; 2005. p. 275–91.Google Scholar
  7. Klemba M, Gluzman IY, Goldberg DE. A Plasmodium falciparum dipeptidyl aminopeptidase participates in vacuolar hemoglobin degradation. J Biol Chem. 2004;279:43000–7.PubMedCrossRefGoogle Scholar
  8. Klonis N, Crespo-Ortiz MP, Bottova I, Abu-Baker N, Kenny S, Rosenthal PJ, Tilley L. Artemisinin activity against Plasmodium falciparum requires hemoglobin uptake and digestion. Proc Natl Acad Sci U S A. 2011;108:11405–10.PubMedCentralPubMedCrossRefGoogle Scholar
  9. Mallari JP, Goldberg DE. Falcilysins. In: Rawlings ND, Salvesen GS, editors. Handbook of proteolytic enzymes. Oxford: Academic; 2013. p. 1459–61.CrossRefGoogle Scholar
  10. Marco M, Coterón JM. Falcipain inhibition as a promising antimalarial target. Curr Top Med Chem. 2012;12(5):408–44.PubMedCrossRefGoogle Scholar
  11. Myers MJ, Goldberg DE. Recent advances in plasmepsin medicinal chemistry and implications for future antimalarial drug discovery efforts. Curr Top Med Chem. 2012;12:445–55.CrossRefGoogle Scholar
  12. Ragheb D, Bompiani KM, Dalal S, Klemba M. Evidence for catalytic roles for Plasmodium falciparum aminopeptidase P in the food vacuole and cytosol. J Biol Chem. 2009;284:24806–15.PubMedCentralPubMedCrossRefGoogle Scholar
  13. Ragheb D, Dalal S, Bompiani KM, Ray WK, Klemba M. Distribution and biochemical properties of an M1-family aminopeptidase in Plasmodium falciparum indicate a role in vacuolar hemoglobin catabolism. J Biol Chem. 2011;286:27255–65.PubMedCentralPubMedCrossRefGoogle Scholar
  14. Rosenthal PJ. Hydrolysis of erythrocyte proteins by proteases of malaria parasites. Curr Opin Hematol. 2002;9:140–5.PubMedCrossRefGoogle Scholar
  15. Rosenthal PJ. Falcipains and other cysteine proteases of malaria parasites. In: Robinson MW, Dalton JP, editors. Cysteine proteases of pathogenic organisms. Austin/New York: Landes Bioscience/Springer Science; 2011. p. 30–48. (Adv Exp Med Biol. 2011; 712: 30–48).CrossRefGoogle Scholar
  16. Rosenthal PJ. Falcipains. In: Rawlings ND, Salvesen GS, editors. Handbook of proteolytic enzymes. Oxford: Academic; 2013. p. 1907–12.CrossRefGoogle Scholar
  17. Rosenthal PJ, et al. J Clin Invest. 1988;82:1560–6.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Division of Biology and Biomedical SciencesWashington UniversitySt. LouisUSA
  2. 2.Department of MedicineSan Francisco General Hospital, University of CaliforniaSan FranciscoUSA