Hemoglobin degradation in the human malaria pathogen Plasmodium falciparum: a catabolic pathway initiated by a specific aspartic protease - PubMed (original) (raw)

Comparative Study

Hemoglobin degradation in the human malaria pathogen Plasmodium falciparum: a catabolic pathway initiated by a specific aspartic protease

D E Goldberg et al. J Exp Med. 1991.

Abstract

Hemoglobin is an important nutrient source for intraerythrocytic malaria organisms. Its catabolism occurs in an acidic digestive vacuole. Our previous studies suggested that an aspartic protease plays a key role in the degradative process. We have now isolated this enzyme and defined its role in the hemoglobinolytic pathway. Laser desorption mass spectrometry was used to analyze the proteolytic action of the purified protease. The enzyme has a remarkably stringent specificity towards native hemoglobin, making a single cleavage between alpha 33Phe and 34Leu. This scission is in the hemoglobin hinge region, unraveling the molecule and exposing other sites for proteolysis. The protease is inhibited by pepstatin and has NH2-terminal homology to mammalian aspartic proteases. Isolated digestive vacuoles make a pepstatin-inhibitable cleavage identical to that of the purified enzyme. The pivotal role of this aspartic hemoglobinase in initiating hemoglobin degradation in the malaria parasite digestive vacuoles is demonstrated.

PubMed Disclaimer

Similar articles

• Order and specificity of the Plasmodium falciparum hemoglobin degradation pathway.
  Gluzman IY, Francis SE, Oksman A, Smith CE, Duffin KL, Goldberg DE. Gluzman IY, et al. J Clin Invest. 1994 Apr;93(4):1602-8. doi: 10.1172/JCI117140. J Clin Invest. 1994. PMID: 8163662 Free PMC article.
• Biosynthesis and maturation of the malaria aspartic hemoglobinases plasmepsins I and II.
  Francis SE, Banerjee R, Goldberg DE. Francis SE, et al. J Biol Chem. 1997 Jun 6;272(23):14961-8. doi: 10.1074/jbc.272.23.14961. J Biol Chem. 1997. PMID: 9169469
• Generation of hemoglobin peptides in the acidic digestive vacuole of Plasmodium falciparum implicates peptide transport in amino acid production.
  Kolakovich KA, Gluzman IY, Duffin KL, Goldberg DE. Kolakovich KA, et al. Mol Biochem Parasitol. 1997 Aug;87(2):123-35. doi: 10.1016/s0166-6851(97)00062-5. Mol Biochem Parasitol. 1997. PMID: 9247924
• Hemoglobin metabolism in the malaria parasite Plasmodium falciparum.
  Francis SE, Sullivan DJ Jr, Goldberg DE. Francis SE, et al. Annu Rev Microbiol. 1997;51:97-123. doi: 10.1146/annurev.micro.51.1.97. Annu Rev Microbiol. 1997. PMID: 9343345 Review.
• Plasmodial hemoglobin degradation: an ordered pathway in a specialized organelle.
  Goldberg DE. Goldberg DE. Infect Agents Dis. 1992 Aug;1(4):207-11. Infect Agents Dis. 1992. PMID: 1365547 Review.

Cited by

• The Digestive Vacuole of the Malaria Parasite: A Specialized Lysosome.
  Wiser MF. Wiser MF. Pathogens. 2024 Feb 20;13(3):182. doi: 10.3390/pathogens13030182. Pathogens. 2024. PMID: 38535526 Free PMC article. Review.
• PTEX helps efficiently traffic haemoglobinases to the food vacuole in Plasmodium falciparum.
  Jonsdottir TK, Elsworth B, Cobbold S, Gabriela M, Ploeger E, Parkyn Schneider M, Charnaud SC, Dans MG, McConville M, Bullen HE, Crabb BS, Gilson PR. Jonsdottir TK, et al. PLoS Pathog. 2023 Jul 31;19(7):e1011006. doi: 10.1371/journal.ppat.1011006. eCollection 2023 Jul. PLoS Pathog. 2023. PMID: 37523385 Free PMC article.
• The ability of Interleukin-10 to negate haemozoin-related pro-inflammatory effects has the potential to restore impaired macrophage function associated with malaria infection.
  Tembo D, Harawa V, Tran TC, Afran L, Molyneux ME, Taylor TE, Seydel KB, Nyirenda T, Russell DG, Mandala W. Tembo D, et al. Malar J. 2023 Apr 14;22(1):125. doi: 10.1186/s12936-023-04539-w. Malar J. 2023. PMID: 37060041 Free PMC article.
• Targeting the Plasmodium falciparum proteome and organelles for potential antimalarial drug candidates.
  Abugri J, Ayariga J, Sunwiale SS, Wezena CA, Gyamfi JA, Adu-Frimpong M, Agongo G, Dongdem JT, Abugri D, Dinko B. Abugri J, et al. Heliyon. 2022 Aug;8(8):e10390. doi: 10.1016/j.heliyon.2022.e10390. Epub 2022 Aug 24. Heliyon. 2022. PMID: 36033316 Free PMC article. Review.
• The natural function of the malaria parasite's chloroquine resistance transporter.
  Shafik SH, Cobbold SA, Barkat K, Richards SN, Lancaster NS, Llinás M, Hogg SJ, Summers RL, McConville MJ, Martin RE. Shafik SH, et al. Nat Commun. 2020 Aug 6;11(1):3922. doi: 10.1038/s41467-020-17781-6. Nat Commun. 2020. PMID: 32764664 Free PMC article.

References

1. 1. Anal Biochem. 1981 Nov 15;118(1):197-203 - PubMed
2. 1. Parasitology. 1980 Apr;80(2):323-30 - PubMed
3. 1. Antimicrob Agents Chemother. 1982 May;21(5):819-22 - PubMed
4. 1. J Parasitol. 1982 Dec;68(6):1068-71 - PubMed
5. 1. Comp Biochem Physiol B. 1983;74(3):559-66 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Europe PubMed Central
  • Ovid Technologies, Inc.
  • PubMed Central
  • Silverchair Information Systems

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Molecular Biology Databases

  • BioCyc
  • Gene Ontology