Erythrocytic adenosine monophosphate as an alternative purine source in Plasmodium falciparum.
Plasmodium falciparum is a purine auxotroph, salvaging purines from erythrocytes for synthesis of RNA and DNA. Hypoxanthine is the key precursor for purine metabolism in Plasmodium. Inhibition of hypoxanthine-forming reactions in both erythrocytes and parasites is lethal to cultured P. falciparum. We observed that high concentrations of adenosine can rescue cultured parasites from purine nucleoside phosphorylase and adenosine deaminase blockade but not when erythrocyte adenosine kinase is also inhibited. P. falciparum lacks adenosine kinase but can salvage AMP synthesized in the erythrocyte cytoplasm to provide purines when both human and Plasmodium purine nucleoside phosphorylases and adenosine deaminases are inhibited. Transport studies in Xenopus laevis oocytes expressing the P. falciparum nucleoside transporter PfNT1 established that this transporter does not transport AMP. These metabolic patterns establish the existence of a novel nucleoside monophosphate transport pathway in P. falciparum.
Cassera
María B
MB
Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York 10461, USA.
Hazleton
Keith Z
KZ
Riegelhaupt
Paul M
PM
Merino
Emilio F
EF
Luo
Minkui
M
Akabas
Myles H
MH
Schramm
Vern L
VL
D000241:Adenosine / Q000737:chemistry; D000244:Adenosine Diphosphate / Q000737:chemistry; D000249:Adenosine Monophosphate / Q000737:chemistry*; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology*; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D009705:Nucleosides / Q000737:chemistry; D009865:Oocytes / Q000378:metabolism; D010963:Plasmodium falciparum / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011687:Purines / Q000737:chemistry*; D014982:Xenopus laevis
D009705:Nucleosides; D011687:Purines; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000241:Adenosine; C030985:purine
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