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Review
. 2008 Aug;7(8):1231-7.
doi: 10.1128/EC.00159-08. Epub 2008 Jun 20.

Purine salvage pathways in the intraerythrocytic malaria parasite Plasmodium falciparum

Megan J Downie  1 , Kiaran Kirk, Choukri Ben Mamoun
Affiliations
Review

Purine salvage pathways in the intraerythrocytic malaria parasite Plasmodium falciparum

Megan J Downie et al. Eukaryot Cell. 2008 Aug.
No abstract available

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Figures

FIG. 1.
FIG. 1.
Purine metabolism within the infected erythrocyte. Inosine is produced from adenosine by ADA. Inosine is then converted to hypoxanthine by PNP). hADA and hPNP are present in the red blood cell cytoplasm, while the parasite ADA (PfADA) and PNP (PfPNP) are active in the parasite cytosol. Both PfADA and PfPNP are capable of acting on 5′-substituted compounds, and so the parasite is able to salvage purines from the polyamine biosynthesis pathway (58, 60). Ado, Ino, Hxt, Guo, Gua, Xan, and Ade are transported across the parasite plasma membrane by PfNT1. Adenine also enters the cell via a second, PfNT1-independent mechanism. Adenine may be metabolized to other nucleosides/nucleobases (Ns/Nb) in the erythrocyte cytoplasm. PRT activity converts hypoxanthine to IMP, guanine to GMP, and xanthine to XMP. IMP, GMP, and XMP are then converted to guanylate and adenylate nucleotides by the action of several more enzymes, outlined in the text and in Fig. 2. There is some evidence to suggest that the parasite can also convert adenine to AMP by using a parasite-encoded APRT (PfAPRT). Abbreviations: Ado, adenosine; Ino, inosine; Hxt, hypoxanthine; Guo, guanosine; Gua, guanine; Xan, xanthine; Ade, adenine; PRPP, phosphoribosylpyrophosphate; RBC, red blood cell; PV, parasitophorous vacuole; MTA, methylthioadenosine; MTI, methylthioinosine.
FIG. 2.
FIG. 2.
Nucleotide production in P. falciparum. Hypoxanthine, which is both transported into the cytoplasm from plasma and produced from adenosine and inosine metabolism (indicated by multiple arrows; see Fig. 1 for more detail), is converted to IMP by PfHGXPRT. IMP can then be converted to adenylate or guanylate nucleotides. To make adenylate nucleotides, IMP is converted to adenylosuccinate by adenylosuccinate synthetase. Adenylosuccinate lyase then converts adenylosuccinate to AMP. AMP is phosphorylated to ADP (by adenylate kinase). Alternatively, IMP can be converted to XMP by IMP dehydrogenase. XMP (which can also be produced directly from xanthine by PfHGXPRT) is converted to GMP by GMP synthetase. GMP can also be produced from guanine by PfHGXPRT. Guanylate kinase phosphorylates GMP to form GDP. Both GDP and ADP are then converted to the NTP or deoxynucleoside triphosphates used in nucleic acid synthesis. PRPP, phosphoribosylpyrophosphate; RBC, red blood cell; PV, parasitophorous vacuole.
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References

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