title: A comprehensive model of purine uptake by the malaria parasite Plasmodium falciparum: identification of four purine transport activities in intraerythrocytic parasites.
abstract: Plasmodium falciparum is incapable of de novo purine biosynthesis, and is absolutely dependent on transporters to salvage purines from the environment. Only one low-affinity adenosine transporter has been characterized to date. In the present study we report a comprehensive study of purine nucleobase and nucleoside transport by intraerythrocytic P. falciparum parasites. Isolated trophozoites expressed (i) a high-affinity hypoxanthine transporter with a secondary capacity for purine nucleosides, (ii) a separate high-affinity transporter for adenine, (iii) a low-affinity adenosine transporter, and (iv) a low-affinity/high-capacity adenine carrier. Hypoxanthine was taken up with 12-fold higher efficiency than adenosine. Using a parasite clone with a disrupted PfNT1 (P. falciparum nucleoside transporter 1) gene we found that the high-affinity hypoxanthine/nucleoside transport activity was completely abolished, whereas the low-affinity adenosine transport activity was unchanged. Adenine transport was increased, presumably to partly compensate for the loss of the high-affinity hypoxanthine transporter. We thus propose a model for purine salvage in P. falciparum, based on the highly efficient uptake of hypoxanthine by PfNT1 and a high capacity for purine nucleoside uptake by a lower affinity carrier.
authors.affiliation: Institute of Biomedical and Life Sciences, Division of Infection and Immunity, Glasgow G12 8TA, Scotland, UK.
authors.forename: Neils B
authors.initials: NB
authors.lastname: Quashie
authors.forename: Dominique
authors.initials: D
authors.lastname: Dorin-Semblat
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Bray
authors.forename: Giancarlo A
authors.initials: GA
authors.lastname: Biagini
authors.forename: Christian
authors.initials: C
authors.lastname: Doerig
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Ranford-Cartwright
authors.forename: Harry P
authors.initials: HP
authors.lastname: De Koning
mesh_terms: D000818:Animals; D001692:Biological Transport; D004912:Erythrocytes / Q000469:parasitology*; D008954:Models, Biological; D015394:Molecular Structure; D033703:Nucleoside Transport Proteins / Q000378:metabolism; D010963:Plasmodium falciparum / Q000378:metabolism*; D011687:Purines / Q000737:chemistry / Q000378:metabolism*; D053058:Trophozoites / Q000378:metabolism
chemical_list: D033703:Nucleoside Transport Proteins; D011687:Purines; C030985:purine