Branched tricarboxylic acid metabolism in Plasmodium falciparum

Kellen L. Olszewski, Michael W. Mather, Joanne M. Morrisey, Benjamin A. Garcia, Akhil B. Vaidya, Joshua D. Rabinowitz and Manuel Llinás ()
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Kellen L. Olszewski: Princeton University
Michael W. Mather: Center for Molecular Parasitology, Drexel University College of Medicine
Joanne M. Morrisey: Center for Molecular Parasitology, Drexel University College of Medicine
Benjamin A. Garcia: Princeton University
Akhil B. Vaidya: Center for Molecular Parasitology, Drexel University College of Medicine
Joshua D. Rabinowitz: Princeton University
Manuel Llinás: Princeton University

Nature, 2010, vol. 466, issue 7307, 774-778

Abstract: No cycling in malaria parasite The tricarboxylic acid (TCA) cycle is a central hub of carbon metabolism, connecting glycolysis, gluconeogenesis, respiration, amino-acid synthesis and other biosynthetic pathways. TCA metabolism in the malaria parasite Plasmodium falciparum is now shown to be largely disconnected from glycolysis, and is organized along fundamentally different lines. In the parasite, glutamine and glutamate are the principal carbon sources for TCA metabolism in a pathway that is branched rather than cyclic. Glucose-derived carbon is virtually absent from the pathway. The results provide a mechanistic explanation for many long-standing observations regarding basic central carbon metabolism in Plasmodium spp., and suggest new targets for antimalarial therapeutic intervention.

Date: 2010
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DOI: 10.1038/nature09301

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