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A comprehensive model of purine uptake by the malaria parasite Plasmodium falciparum: identification of four purine transport activities in intraerythrocytic parasites

Quashie, N. B., Dorin-Semblat, D., Bray, Patrick, Biagini, Giancarlo, Doerig, C., Ranford-Cartwright, L. C. and de Koning, H. P. (2008) 'A comprehensive model of purine uptake by the malaria parasite Plasmodium falciparum: identification of four purine transport activities in intraerythrocytic parasites'. Biochemical Journal, Vol 411, Issue 2, pp. 287-295.

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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.

Item Type: Article
Additional Information: Part 2
Uncontrolled Keywords: drug target equilibrative nucleoside transporter family nucleobase transporter pfnt1 plasmodium falciparum purine salvage pfnt1 nucleoside transporter trypanosoma-brucei-brucei adenosine transporter toxoplasma-gondii plasma-membrane nucleobase transport adenine phosphoribosyltransferase substrate recognition leishmania-donovani allopurinol uptake
Subjects: WC Communicable Diseases > Tropical and Parasitic Diseases > WC 680 Tropical diseases (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors
WB Practice of Medicine > Medical Climatology > WB 710 Diseases of geographic areas
QX Parasitology > QX 20 Research (General)
QX Parasitology > QX 4 General works
QX Parasitology > Protozoa > QX 135 Plasmodia
QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes
QX Parasitology > QX 45 Host-parasite relations
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 695 Parasitic diseases (General)
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1042/BJ20071460
Depositing User: Mary Creegan
Date Deposited: 26 Mar 2010 17:00
Last Modified: 06 Feb 2018 13:00
URI: http://archive.lstmed.ac.uk/id/eprint/899

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