Ann. N.Y. Acad. Sci. ISSN 0077-8923
A N N A L S O F T H E N E W Y O R K A C A D E M Y O F SC I E N C E S Issue: Malaria: Advances in Pathophysiology, Biology, and Drug Development
Purine import into malaria parasites as a target for antimalarial drug development I. J. Frame,1,∗ Roman Deniskin,1,∗ Avish Arora,1 and Myles H. Akabas1,2,3 1 Department of Physiology and Biophysics, 2 Department of Neuroscience, 3 Department of Medicine, Albert Einstein College of Medicine, Bronx, New York
Address for correspondence: Myles H. Akabas, M.D., Ph.D., Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. [email protected]
Infection with Plasmodium species parasites causes malaria. Plasmodium parasites are purine auxotrophs. In all life cycle stages, they require purines for RNA and DNA synthesis and other cellular metabolic processes. Purines are imported from the host erythrocyte by equilibrative nucleoside transporters (ENTs). They are processed via purine salvage pathway enzymes to form the required purine nucleotides. The Plasmodium falciparum genome encodes four putative ENTs (PfENT1–4). Genetic, biochemical, and physiologic evidence suggest that PfENT1 is the primary purine transporter supplying the purine salvage pathway. Protein mass spectrometry shows that PfENT1 is expressed in all parasite stages. PfENT1 knockout parasites are not viable in culture at purine concentrations found in human blood (
A N N A L S O F T H E N E W Y O R K A C A D E M Y O F SC I E N C E S Issue: Malaria: Advances in Pathophysiology, Biology, and Drug Development
Purine import into malaria parasites as a target for antimalarial drug development I. J. Frame,1,∗ Roman Deniskin,1,∗ Avish Arora,1 and Myles H. Akabas1,2,3 1 Department of Physiology and Biophysics, 2 Department of Neuroscience, 3 Department of Medicine, Albert Einstein College of Medicine, Bronx, New York
Address for correspondence: Myles H. Akabas, M.D., Ph.D., Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. [email protected]
Infection with Plasmodium species parasites causes malaria. Plasmodium parasites are purine auxotrophs. In all life cycle stages, they require purines for RNA and DNA synthesis and other cellular metabolic processes. Purines are imported from the host erythrocyte by equilibrative nucleoside transporters (ENTs). They are processed via purine salvage pathway enzymes to form the required purine nucleotides. The Plasmodium falciparum genome encodes four putative ENTs (PfENT1–4). Genetic, biochemical, and physiologic evidence suggest that PfENT1 is the primary purine transporter supplying the purine salvage pathway. Protein mass spectrometry shows that PfENT1 is expressed in all parasite stages. PfENT1 knockout parasites are not viable in culture at purine concentrations found in human blood (
