A comprehensive model of purine uptake by the malaria parasite Plasmodium falciparum: identification of four purine transport activities in intraerythrocytic parasites.
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.
Quashie
Neils B
NB
Institute of Biomedical and Life Sciences, Division of Infection and Immunity, Glasgow G12 8TA, Scotland, UK.
Dorin-Semblat
Dominique
D
Bray
Patrick G
PG
Biagini
Giancarlo A
GA
Doerig
Christian
C
Ranford-Cartwright
Lisa C
LC
De Koning
Harry P
HP
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
D033703:Nucleoside Transport Proteins; D011687:Purines; C030985:purine