Schematic representation of the pathways involved in the uptake of the essential amino acid isoleucine in P falciparum–infected erythrocytes. Under physiologic conditions isoleucine enters infected cells via a combination of the endogenous erythrocyte L system (20%) and the parasite-induced NPPs (80%). On entering the infected cell isoleucine is taken up, across the parasite plasma membrane, via a saturable (K_m = 550 μM) transporter that facilitates the influx of isoleucine (the one amino acid absent from adult hemoglobin) in exchange for leucine which is 1 of the 2 most abundant amino acids in adult hemoglobin and which is liberated within the parasite via the degradation of hemoglobin in the digestive vacuole. On entering the parasite isoleucine is incorporated into protein, as well as sequestered via a high-affinity (K_m = 0.9 μM), ATP-dependent mechanism (indicated by the question mark) which may involve the metabolic trapping of isoleucine derivatives within the parasite and/or the accumulation of the amino acid within a parasite organelle. RBC indicates red blood cell; PV, parasitophorous vacuole; Hb, hemoglobin.