ArticleThe Journal of biological chemistry2013
Kinetic flux profiling elucidates two independent acetyl-CoA biosynthetic pathways in Plasmodium falciparum.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 95 citations in OpenAlex.
- Article
- Acyl Carrier Protein is Essential for Apicoplast Biogenesis in Malaria Parasites Independent of Fatty Acid Synthesis.bioRxiv : the preprint server for biology · 2026Article
- An endoplasmic reticulum localized acetyl-CoA transporter is required for efficient fatty acid synthesis inOpen biology · 2024Article
- Apicoplast-derived isoprenoids are essential for biosynthesis of GPI protein anchors, and consequently for egress and invasion in Plasmodium falciparum.PLoS pathogens · 2024Article
- Transmission-Blocking Strategies for Malaria Eradication: Recent Advances in Small-Molecule Drug Development.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Purinergic Receptor Antagonists Inhibit Hemolysis Induced byPathogens (Basel, Switzerland) · 2024Article
- M-iScience · 2024Article
- Hungry for control: metabolite signaling to chromatin in Plasmodium falciparum.Current opinion in microbiology · 2024Review
- The interdependence of isoprenoid synthesis and apicoplast biogenesis in malaria parasites.PLoS pathogens · 2023Article
- Susceptibility of Ugandan Plasmodium falciparum Isolates to the Antimalarial Drug Pipeline.Microbiology spectrum · 2023Article
- The mitochondrion ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Toxoplasma metabolic flexibility in different growth conditions.Trends in parasitology · 2022Review
- 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
- A new mass spectral library for high-coverage and reproducible analysis of the Plasmodium falciparum-infected red blood cell proteome.GigaScience · 2022Article
- Chemogenomics identifies acetyl-coenzyme A synthetase as a target for malaria treatment and prevention.Cell chemical biology · 2022Article
- Pantothenate and CoA biosynthesis in Apicomplexa and their promise as antiparasitic drug targets.PLoS pathogens · 2021Review
- The Kringle of Life.The protein journal · 2021Article
- Linking nutrient sensing and gene expression in Plasmodium falciparum blood-stage parasites.Molecular microbiology · 2021Review
- 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
- Roles of Ferredoxin-Dependent Proteins in the Apicoplast of Plasmodium falciparum Parasites.mBio · 2021Article
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
The malaria parasite Plasmodium falciparum depends on glucose to meet its energy requirements during blood-stage development. Although glycolysis is one of the best understood pathways in the parasite, it is unclear if glucose metabolism appreciably contributes to the acetyl-CoA pools required for tricarboxylic acid metabolism (TCA) cycle and fatty acid biosynthesis. P. falciparum possesses a pyruvate dehydrogenase (PDH) complex that is localized to the apicoplast, a specialized quadruple membrane organelle, suggesting that separate acetyl-CoA pools are likely. Herein, we analyze PDH-deficient parasites using rapid stable-isotope labeling and show that PDH does not appreciably contribute to acetyl-CoA synthesis, tricarboxylic acid metabolism, or fatty acid synthesis in blood stage parasites. Rather, we find that acetyl-CoA demands are supplied through a "PDH-like" enzyme and provide evidence that the branched-chain keto acid dehydrogenase (BCKDH) complex is performing this function. We also show that acetyl-CoA synthetase can be a significant contributor to acetyl-CoA biosynthesis. Interestingly, the PDH-like pathway contributes glucose-derived acetyl-CoA to the TCA cycle in a stage-independent process, whereas anapleurotic carbon enters the TCA cycle via a stage-dependent phosphoenolpyruvate carboxylase/phosphoenolpyruvate carboxykinase process that decreases as the parasite matures. Although PDH-deficient parasites have no blood-stage growth defect, they are unable to progress beyond the oocyst phase of the parasite mosquito stage.
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