Biddau, M. and Müller, S. (2016) Carbon metabolism of Plasmodium falciparum. In: Müller, S., Cerdan, R. and Radulescu, O. (eds.) Comprehensive Analysis of Parasite Biology: From Metabolism to Drug Discovery. Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, pp. 371-398. ISBN 9783527339044 (doi: 10.1002/9783527694082.ch16)
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Abstract
Carbon metabolism of Plasmodium has attracted renewed interest. Advanced reverse genetics and analytical technologies allowed dissecting intermediary carbon metabolism of malaria parasites and assessing and validating its suitability for drug discovery. It was corroborated that anaerobic glycolysis is the major energy-generating pathway during intraerythrocytic life of the parasites while sexual development appears to rely much more on mitochondrial activity. The roles of parasite-specific metabolic adaptations such as carbon dioxide fixation via phosphoenolpyruvate carboxylase will be discussed especially as this diversion from glycolysis is indispensable for the human malaria parasite Plasmodium falciparum at least in vitro. It is well established that maintaining the electrochemical gradient across the inner mitochondrial membrane is vital for parasite survival, and atovaquone in combination with proguanil is the antimalarial in clinical use that takes advantage of the essential function of the mitochondrial electron transport chain. Other essential pathways suitable for drug discovery linked to carbon metabolism are those found in the parasite's plastid-like organelle, the apicoplast. The most promising is the biosynthesis of isopentenyl-pyrophosphate, which has been identified as the raison d'être of the organelle. Other targets, which affect liver-stage development of the parasites when inhibited, are the type II fatty acid biosynthesis (FASII) and the pyruvate dehydrogenase complex (PDC) present in the organelle, and it has been suggested that sexual development in the mosquito is affected by the loss of FAS II and PDC in the human malaria species P. falciparum.
| Item Type: | Book Sections |
|---|---|
| Status: | Published |
| Glasgow Author(s) Enlighten ID: | Biddau, Dr Marco and Muller, Professor Sylke |
| Authors: | Biddau, M., and Müller, S. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Publisher: | Wiley-VCH Verlag GmbH & Co. KGaA |
| ISBN: | 9783527339044 |
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