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The genome of Plasmodium falciparum indicates that the metabolic pathways utilized by this organism are highly unique. Recent efforts to comprehensively examine the biology of P. falciparum have focused on transcriptome and proteome analysis to gain insight into Plasmodium -specific pathways. The third crucial component that remains to be established is the metabolome: the complement of small-molecule metabolites and their relative levels. Our lab has begun to characterize various aspects of parasite metabolism using high accuracy mass-spectrometry to simultaneously measure metabolites from complex cellular extracts from parasite-infected cells. The approaches we are using allow us to assay various aspects of the P. falciparum metabolome. One approach has been to examine the interaction of Plasmodium with the host red blood cell using targeted measurements of specific metabolites shared with the host erythrocyte. We are also using 13C and 15N isotopic labeling experiments to directly trace carbon flux through known biochemical pathways. Finally, we are using metabolite measurements to map genetic control of metabolism by assaying global metabolite patterns in the parents and progeny of a Plasmodium falciparum genetic cross. Results from these studies are beginning to unravel the divergence of metabolism in P. falciparum and promise to provide unique avenues for future drug intervention strategies.
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