title: Sequestration and metabolism of host cell arginine by the intraerythrocytic malaria parasite Plasmodium falciparum.
abstract: Human erythrocytes have an active nitric oxide synthase, which converts arginine into citrulline and nitric oxide (NO). NO serves several important functions, including the maintenance of normal erythrocyte deformability, thereby ensuring efficient passage of the red blood cell through narrow microcapillaries. Here, we show that following invasion by the malaria parasite Plasmodium falciparum the arginine pool in the host erythrocyte compartment is sequestered and metabolized by the parasite. Arginine from the extracellular medium enters the infected cell via endogenous host cell transporters and is taken up by the intracellular parasite by a high-affinity cationic amino acid transporter at the parasite surface. Within the parasite arginine is metabolized into citrulline and ornithine. The uptake and metabolism of arginine by the parasite deprive the erythrocyte of the substrate required for NO production and may contribute to the decreased deformability of infected erythrocytes.
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, 08544, USA.|Research School of Biology, The Australian National University, Canberra, ACT, 2601, Australia.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Cobbold
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, 08544, USA.|Department of Molecular Biology, Princeton University, Princeton, NJ, 08544, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Llinás
authors.affiliation: Research School of Biology, The Australian National University, Canberra, ACT, 2601, Australia.
authors.forename: Kiaran
authors.initials: K
authors.lastname: Kirk
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001120:Arginine / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D006790:Host-Parasite Interactions; D006801:Humans; D010963:Plasmodium falciparum / Q000472:pathogenicity*
chemical_list: D000255:Adenosine Triphosphate; D001120:Arginine