Fig. 5

Increased Flux in Folate Metabolism in Response to Chloroquine. Illustration of folate metabolism reactions showing increases in flux levels in both chloroquine-treated models versus untreated models. We predict a shift in 4-aminobenzoate acquisition between short- and long-term chloroquine treatment, and elevated flux through all downstream steps of folate metabolism. Clinically available drugs target this pathway (sulfadoxine and pyrimethamine, indicated in red). Both enzymes targeted by these antimalarials (dihydropteroate synthase and dihydrofolate reductase) carry increased flux in both models of short- and long-term chloroquine treatment. Connectivity to other metabolic pathways are shown (dotted lines)