Submitted November 2, 2005
Accepted October 12, 2006
Transport of the essential nutrient isoleucine in human
erythrocytes infected with the malaria parasite
Plasmodium falciparum
Rowena E Martin and Kiaran Kirk*
School of Biochemistry and Molecular Biology, The Australian National University, Canberra, Australia
* Corresponding author; email: kiaran.kirk{at}anu.edu.au.
The intraerythrocytic malaria parasite derives much of its requirement for amino acids from the digestion of the haemoglobin of its host cell. However one amino acid, isoleucine, is absent from adult human hemoglobin and must therefore be obtained from the extracellular medium. In this study we have characterised the mechanisms involved in the uptake of isoleucine by the intraerythrocytic parasite. Under physiological conditions the rate of transport of isoleucine into human erythrocytes infected with mature 'trophozoite-stage' P. falciparum parasites is increased to approximately five-fold that in uninfected cells, with the increased flux being via the 'new permeability pathways' (NPP) induced by the parasite in the host cell membrane. Transport via the NPP ensures that protein synthesis is not rate-limited by the flux of isoleucine across the erythrocyte membrane. On entering the infected erythrocyte, isoleucine is taken up into the parasite via a saturable, ATP-, Na+-, and H+-independent system which has the capacity to mediate the influx of isoleucine in exchange for leucine (liberated from hemoglobin). The accumulation of radiolabelled isoleucine within the parasite is mediated by a second (high-affinity, ATP-dependent) mechanism, perhaps
involving metabolism and/or the concentration of isoleucine within an intracellular organelle.
