ArticlePLoS pathogens2014
Phosphoenolpyruvate carboxylase identified as a key enzyme in erythrocytic Plasmodium falciparum carbon metabolism.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 52 citations in OpenAlex.
- Integrative genomics ofbioRxiv : the preprint server for biology · 2026Article
- Purinergic Receptor Antagonists Inhibit Hemolysis Induced byPathogens (Basel, Switzerland) · 2024Article
- Cell-cell heterogeneity in phosphoenolpyruvate carboxylase biases early cell fate priming inFrontiers in cell and developmental biology · 2024Article
- Metabolic changes accompanying the loss of fumarate hydratase and malate-quinone oxidoreductase in the asexual blood stage of Plasmodium falciparum.The Journal of biological chemistry · 2022Article
- Plasmodium falciparum LipB mutants display altered redox and carbon metabolism in asexual stages and cannot complete sporogony in Anopheles mosquitoes.International journal for parasitology · 2021Article
- Article
- β-Carboline Derivatives Tackling Malaria: Biological Evaluation and Docking Analysis.ACS omega · 2020Article
- Metabolic alterations in the erythrocyte during blood-stage development of the malaria parasite.Malaria journal · 2020Article
- Contribution of the precursors and interplay of the pathways in the phospholipid metabolism of the malaria parasite.Journal of lipid research · 2018Article
- Using a genome-scale metabolic network model to elucidate the mechanism of chloroquine action in Plasmodium falciparum.International journal for parasitology. Drugs and drug resistance · 2017Article
- Suppression of experimental cerebral malaria by disruption of malate:quinone oxidoreductase.Malaria journal · 2017Article
- Article
- A Novel Methodology for Bioenergetic Analysis of Plasmodium falciparum Reveals a Glucose-Regulated Metabolic Shift and Enables Mode of Action Analyses of Mitochondrial Inhibitors.ACS infectious diseases · 2016Article
- Stage-Specific Changes in Plasmodium Metabolism Required for Differentiation and Adaptation to Different Host and Vector Environments.PLoS pathogens · 2016Article
- A suggested vital function for eIF-5A and dhs genes during murine malaria blood-stage infection.FEBS open bio · 2016Article
- Recent advances in understanding apicomplexan parasites.F1000Research · 2016Review
- Role and Regulation of Glutathione Metabolism in Plasmodium falciparum.Molecules (Basel, Switzerland) · 2015Review
- Host reticulocytes provide metabolic reservoirs that can be exploited by malaria parasites.PLoS pathogens · 2015Article
- Genetic investigation of tricarboxylic acid metabolism during the Plasmodium falciparum life cycle.Cell reports · 2015Article
- Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose.PLoS pathogens · 2015Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Phospoenolpyruvate carboxylase (PEPC) is absent from humans but encoded in the Plasmodium falciparum genome, suggesting that PEPC has a parasite-specific function. To investigate its importance in P. falciparum, we generated a pepc null mutant (D10(Δpepc) ), which was only achievable when malate, a reduction product of oxaloacetate, was added to the growth medium. D10(Δpepc) had a severe growth defect in vitro, which was partially reversed by addition of malate or fumarate, suggesting that pepc may be essential in vivo. Targeted metabolomics using (13)C-U-D-glucose and (13)C-bicarbonate showed that the conversion of glycolytically-derived PEP into malate, fumarate, aspartate and citrate was abolished in D10(Δpepc) and that pentose phosphate pathway metabolites and glycerol 3-phosphate were present at increased levels. In contrast, metabolism of the carbon skeleton of (13)C,(15)N-U-glutamine was similar in both parasite lines, although the flux was lower in D10(Δpepc); it also confirmed the operation of a complete forward TCA cycle in the wild type parasite. Overall, these data confirm the CO2 fixing activity of PEPC and suggest that it provides metabolites essential for TCA cycle anaplerosis and the maintenance of cytosolic and mitochondrial redox balance. Moreover, these findings imply that PEPC may be an exploitable target for future drug discovery.
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