A malarial cysteine proteinase is necessary for hemoglobin degradation by Plasmodium falciparum

Rosenthal, P J; McKerrow, J H; Aikawa, M; Nagasawa, H; Leech, J H

doi:10.1172/jci113766

Cited by 331Malaria Research and ControlProtease and Inhibitor MechanismsErythrocyte Function and Pathophysiology

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A malarial cysteine proteinase is necessary for hemoglobin degradation by Plasmodium falciparum

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Rosenthal, P J, McKerrow, J H, Aikawa, M, Nagasawa, H, Leech, J H·1988·Journal of Clinical Investigation

DOI 10.1172/jci113766PMC PMC442723

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Abstract

To obtain free amino acids for protein synthesis, trophozoite stage malaria parasites feed on the cytoplasm of host erythrocytes and degrade hemoglobin within an acid food vacuole. The food vacuole appears to be analogous to the secondary lysosomes of mammalian cells. To determine the enzymatic mechanism of hemoglobin degradation, we incubated trophozoite-infected erythrocytes with peptide inhibitors of different classes of proteinases. Leupeptin and L-transepoxy-succinyl-leucyl-amido-(4-guanidino)-butane (E-64), two peptide inhibitors of cysteine proteinases, inhibited the proteolysis of globin and caused the accumulation of undegraded erythrocyte cytoplasm in parasite food vacuoles, suggesting that a food vacuole cysteine proteinase is necessary for hemoglobin degradation. Proteinase assays of trophozoites demonstrated cysteine proteinase activity with a pH optimum similar to that of the food vacuole and the substrate specificity of lysosomal cathepsin L. We also identified an Mr 28,000 proteinase that was trophozoite stage-specific and was inhibited by leupeptin and E-64. We conclude that the Mr 28,000 cysteine proteinase has a critical, perhaps rate-limiting, role in hemoglobin degradation within the food vacuole of Plasmodium falciparum. Specific inhibitors of this enzyme might provide new means of antimalarial chemotherapy.

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Malaria parasites degrade HB of host RBC within a food vacuole to obtain free amino acids for protein synthesis.
“To obtain free amino acids for protein synthesis however, malaria parasites degrade HB of host RBC within a food vacuole to obtain free amino acids for protein synthesis (Rosenthal et al., 1988).”
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Authors: Rosenthal, P. J., McKerrow, J. H., Aikawa, M., Nagasawa, H., & Leech, J. H.
Affiliations: San Francisco General Hospital (US)
ORCID: Rosenthal, P J
McKerrow, J H
Leech, J H
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1988-11-01
Volume: 82
Issue: 5
Pages: 1560-1566
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci113766
PMC: PMC442723
OpenAlex: W1976757612
Cited by: 331
References: 38
Citations by year: 2026: 6 · 2025: 3 · 2024: 1 · 2023: 6 · 2022: 5 · 2021: 2 · 2020: 6 · 2019: 7 · 2018: 7 · 2017: 6 · 2016: 6 · 2015: 5 · 2014: 10 · 2013: 11 · 2012: 12
FWCI: 8.79
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Science Foundation (8603689)
National Institute of Allergy and Infectious Diseases (AI 10645, AI-24349)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Health Sciences › Medicine › Physiology (medical) › Erythrocyte Function and Pathophysiology
Keywords: Plasmodium falciparum, cysteine protease, hemoglobin degradation, food vacuoles, trophozoites, leupeptin, E-64, cathepsin L, antimalarial drug targets, peptide inhibitors
MeSH terms: Animals, Cysteine Endopeptidases, Hemoglobins, Leucine, Leupeptins, Malaria, Microscopy, Electron, Molecular Weight, Plasmodium falciparum, Protease Inhibitors

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A malarial cysteine proteinase is necessary for hemoglobin degradation by Plasmodium falciparum

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