Purine nucleobase transport in the intraerythrocytic malaria parasite

Megan J. Downie, Kevin J. Saliba, Stefan Bröer, Susan M. Howitt, Kiaran Kirk*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    34 Citations (Scopus)

    Abstract

    Hypoxanthine, a nucleobase, serves as the major source of the essential purine group for the intraerythrocytic malaria parasite. In this study we have measured the uptake of hypoxanthine, and that of the related purine nucleobase adenine, by mature blood-stage Plasmodium falciparum parasites isolated from their host cells by saponin-permeabilisation of the erythrocyte and parasitophorous vacuole membranes. The uptake of both [3H]hypoxanthine and [3H]adenine was comprised of at least two components; in each case there was a rapid equilibration of the radiolabel between the intra- and extracellular solutions via a low-affinity transport mechanism, and an accumulation of radiolabel (such that the estimated intracellular concentration exceeded the extracellular concentration) via a higher-affinity process. The uptake of [3H]adenine was studied in more detail. The rapid, low-affinity equilibration of [3H]adenine between the intra-and extracellular solution was independent of the energy status of the parasite whereas the higher-affinity accumulation of the radiolabel was ATP-dependent. A kinetic analysis of adenine uptake revealed that the low-affinity (equilibrative) process had a Km of ∼1.2 mM, similar to the value of 0.82 mM estimated here (using the Xenopus laevis oocyte expression system) for the Km for the transport of adenine by PfENT1, a parasite-encoded member of the 'equilibrative nucleoside/nucleobase transporter' family. The results indicate that nucleobases enter the intraerythrocytic parasite via a rapid, equilibrative process that has kinetic characteristics similar to those of PfENT1.

    Original languageEnglish
    Pages (from-to)203-209
    Number of pages7
    JournalInternational Journal for Parasitology
    Volume38
    Issue number2
    DOIs
    Publication statusPublished - Feb 2008

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