Erythrocytic adenosine monophosphate as an alternative purine source in Plasmodium falciparum

María B. Cassera, Keith Z. Hazleton, Paul M. Riegelhaupt, Emilio F. Merino, Minkui Luo, Myles Akabas, Vern L. Schramm

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)32889-32899
Number of pages11
JournalJournal of Biological Chemistry
Volume283
Issue number47
DOIs
StatePublished - Nov 21 2008

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Adenosine Kinase
Purine-Nucleoside Phosphorylase
Salvaging
Purines
Hypoxanthine
Adenosine Deaminase
Adenosine Monophosphate
Plasmodium falciparum
Nucleoside Deaminases
Nucleoside Transport Proteins
Enzyme inhibition
Erythrocytes
Nucleosides
Metabolism
Plasmodium
Adenosine
RNA
Parasites
DNA
Xenopus laevis

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Erythrocytic adenosine monophosphate as an alternative purine source in Plasmodium falciparum. / Cassera, María B.; Hazleton, Keith Z.; Riegelhaupt, Paul M.; Merino, Emilio F.; Luo, Minkui; Akabas, Myles; Schramm, Vern L.

In: Journal of Biological Chemistry, Vol. 283, No. 47, 21.11.2008, p. 32889-32899.

Research output: Contribution to journalArticle

Cassera, María B. ; Hazleton, Keith Z. ; Riegelhaupt, Paul M. ; Merino, Emilio F. ; Luo, Minkui ; Akabas, Myles ; Schramm, Vern L. / Erythrocytic adenosine monophosphate as an alternative purine source in Plasmodium falciparum. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 47. pp. 32889-32899.
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