Methionine transport in the malaria parasite Plasmodium falciparum.
The intraerythrocytic malaria parasite, Plasmodium falciparum, derives amino acids from the digestion of host cell haemoglobin. However, it also takes up amino acids from the extracellular medium. Isoleucine is absent from adult human haemoglobin and an exogenous source of isoleucine is essential for parasite growth. An extracellular source of methionine is also important for the normal growth of at least some parasite strains. In this study we have characterised the uptake of methionine by P. falciparum-infected human erythrocytes, and by parasites functionally isolated from their host cells by saponin-permeabilization of the erythrocyte membrane. Infected erythrocytes take up methionine much faster than uninfected erythrocytes, with the increase attributable to the flux of this amino acid via the New Permeability Pathways induced by the parasite in the erythrocyte membrane. Having entered the infected cell, methionine is taken up by the intracellular parasite via a saturable, temperature-dependent process that is independent of ATP, Na(+) and H(+). Substrate competition studies, and comparison of the transport of methionine with that of isoleucine and leucine, yielded results consistent with the hypothesis that the parasite has at its surface one or more transporters which mediate the flux into and out of the parasite of a broad range of neutral amino acids. These transporters function most efficiently when exchanging one neutral amino acid for another, thus providing a mechanism whereby the parasite is able to import important exogenous amino acids in exchange for surplus neutral amino acids liberated from the digestion of host cell haemoglobin.
Cobbold
Simon A
SA
Research School of Biology, The Australian National University, Canberra, ACT 0200, Australia.
Martin
Rowena E
RE
Kirk
Kiaran
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D026905:Amino Acid Transport Systems / Q000378:metabolism; D001692:Biological Transport; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D006859:Hydrogen / Q000378:metabolism; D007532:Isoleucine / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008715:Methionine / Q000378:metabolism*; D008954:Models, Biological; D010963:Plasmodium falciparum / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism
D026905:Amino Acid Transport Systems; D007532:Isoleucine; D006859:Hydrogen; D000255:Adenosine Triphosphate; D012964:Sodium; D008715:Methionine; D007930:Leucine