Figure 1. Glutamine drives reverse flux through the TCA cycle.

a, Relative concentrations of isotope isomers of carboxylic acids in extracts of P. falciparum-infected RBCs. Synchronized parasite were cultured in medium supplemented with either U-¹³C-glucose or U-¹³C-¹⁵N-glutamine 2 hours prior to invasion, then extracted every 8 hours post invasion (hpi) for HPLC-MS analysis. The plots to the right of the grey triangles zoom in on the profiles of the labeled metabolites. The +3 and +4 malate arises from the reductive and oxidative pathways, respectively, while +3 fumarate likely derives from interconversion of fumarate and malate by fumarate hydratase (PFI1340w). Error bars show the s.d. of n = 3 biological replicates. b, Schematic of the oxidative pathway from 2-oxoglutarate to malate. Red dots denote carbon-13 atoms. c, Schematic of the reductive carboxylation pathway from 2-oxoglutarate to malate. Ac-R represents either acetyl-CoA or acetate.