Glycerol: An unexpected major metabolite of energy metabolism by the human malaria parasite

Abstract Background Malaria is a global health emergency, and yet our understanding of the energy metabolism of the principle causative agent of this devastating disease, Plasmodium falciparum , remains rather basic. Glucose was shown to be an essential nutritional requirement nearly 100 years ago a...

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Bibliographic Details
Published in:Malaria Journal
Main Authors: Bray Patrick G, Fisher Nicholas, Roslaini Abd, Al-Helal Mohammed, Lian Lu-Yun, Ward Stephen A, Biagini Giancarlo A
Format: Article in Journal/Newspaper
Language:English
Published: BMC 2009
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Online Access:https://doi.org/10.1186/1475-2875-8-38
https://doaj.org/article/6c801cea5264442287ef2d72a9ee05a5
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Summary:Abstract Background Malaria is a global health emergency, and yet our understanding of the energy metabolism of the principle causative agent of this devastating disease, Plasmodium falciparum , remains rather basic. Glucose was shown to be an essential nutritional requirement nearly 100 years ago and since this original observation, much of the current knowledge of Plasmodium energy metabolism is based on early biochemical work, performed using basic analytical techniques (e.g. paper chromatography), carried out almost exclusively on avian and rodent malaria. Data derived from malaria parasite genome and transcriptome studies suggest that the energy metabolism of the parasite may be more complex than hitherto anticipated. This study was undertaken in order to further characterize the fate of glucose catabolism in the human malaria parasite, P. falciparum . Methods Products of glucose catabolism were determined by incubating erythrocyte-freed parasites with D-[1- 13 C] glucose under controlled conditions and metabolites were identified using 13 C-NMR spectroscopy. Results Following a 2 h incubation of freed- P. falciparum parasites with 25 mM D-[1- 13 C] glucose ( n = 4), the major metabolites identified included; [3- 13 C] lactate, [1,3- 13 C] glycerol, [3- 13 C] pyruvate, [3- 13 C] alanine and [3- 13 C] glycerol-3-phosphate. Control experiments performed with uninfected erythrocytes incubated under identical conditions did not show any metabolism of D-[1- 13 C] glucose to glycerol or glycerol-3-phosphate. Discussion The identification of glycerol as a major glucose metabolite confirms the view that energy metabolism in this parasite is more complex than previously proposed. It is hypothesized here that glycerol production by the malaria parasite is the result of a metabolic adaptation to growth in O 2 -limited (and CO 2 elevated) conditions by the operation of a glycerol-3-phosphate shuttle for the re-oxidation of assimilatory NADH. Similar metabolic adaptations have been reported previously for other ...