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-[1-13C] glucose under controlled conditions 
and metabolites were identified using 13C-NMR spectroscopy.
RESULTS: Following a 2 h incubation of freed-P. falciparum parasites with 25 mM 
D-[1-13C] glucose (n = 4), the major metabolites identified included; [3-13C] 
lactate, [1,3-13C] glycerol, [3-13C] pyruvate, [3-13C] alanine and [3-13C] 
glycerol-3-phosphate. Control experiments performed with uninfected erythrocytes 
incubated under identical conditions did not show any metabolism of D-[1-13C] 
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 O2-limited 
(and CO2 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 microaerobic/anaerobic organisms, such as 
yeast, rumen protozoa and human parasitic protozoa.
CONCLUSION: These data highlight the need to re-evaluate the carbon and redox 
balance of this important human pathogen, ultimately leading to a better 
understanding of how the parasite is able to adapt to the variable environments 
encountered during parasite development and disease progression.