Purine salvage pathways in the intraerythrocytic malaria parasite Plasmodium falciparum

Abstract

Purines enter the intraerythrocytic malaria parasite via a fast, low-affinity, broad-capacity process that can be attributed primarily to the parasite plasma membrane transporter PfNT1. The reliance of the parasite on PfNT1 makes this protein a worthy target for further investigation, while the determination of the roles played by PfNT2, PfNT3, and PfNT4 in parasite physiology should also prove interesting. Within the parasite, the metabolism of purines appears to be funneled through hypoxanthine by the sequential actions of ADA and PNP, prior to phosphoribosylation of hypoxanthine by PRT. The fact that hypoxanthine is the main purine source found in human serum suggests that PfADA and PfPNP are unlikely to play an essential function under physiological conditions or be considered good drug targets. However, the apparent dependence of the parasite on PfHGXPRT for nucleotide synthesis makes this protein a promising drug target. Efforts to develop compounds that can distinguish between this enzyme and the human counterpart are well justified and may well form the basis for future antimalarial drug strategies. Show more