A comprehensive model of purine uptake by the malaria parasite Plasmodium falciparum: identification of four purine transport activities in intraerythrocytic parasites

The Biochemical Journal
Neils B QuashieHarry P De Koning

Abstract

Plasmodium falciparum is incapable of de novo purine biosynthesis, and is absolutely dependent on transporters to salvage purines from the environment. Only one low-affinity adenosine transporter has been characterized to date. In the present study we report a comprehensive study of purine nucleobase and nucleoside transport by intraerythrocytic P. falciparum parasites. Isolated trophozoites expressed (i) a high-affinity hypoxanthine transporter with a secondary capacity for purine nucleosides, (ii) a separate high-affinity transporter for adenine, (iii) a low-affinity adenosine transporter, and (iv) a low-affinity/high-capacity adenine carrier. Hypoxanthine was taken up with 12-fold higher efficiency than adenosine. Using a parasite clone with a disrupted PfNT1 (P. falciparum nucleoside transporter 1) gene we found that the high-affinity hypoxanthine/nucleoside transport activity was completely abolished, whereas the low-affinity adenosine transport activity was unchanged. Adenine transport was increased, presumably to partly compensate for the loss of the high-affinity hypoxanthine transporter. We thus propose a model for purine salvage in P. falciparum, based on the highly efficient uptake of hypoxanthine by PfNT1 and a high...Continue Reading

References

Aug 20, 1976·Science·W Trager, J B Jensen
Apr 1, 1975·Experimental Parasitology·M S Manandhar, K Van Dyke
Dec 1, 1991·The Journal of Clinical Investigation·P A BermanJ A Freese
Oct 11, 1988·Biochimica Et Biophysica Acta·P G PlagemannC Woffendin
Aug 1, 1972·The Journal of protozoology·S M Tracy, I W Sherman
Feb 1, 1970·The Journal of protozoology·W E Gutteridge, P I Trigg
May 1, 1982·Molecular and Biochemical Parasitology·P ReyesH G Heidrich
Mar 1, 1995·Molecular and Biochemical Parasitology·J C SchwabK A Joiner
Nov 19, 1997·Molecular and Biochemical Parasitology·H P de Koning, S M Jarvis
May 23, 1998·The Journal of Biological Chemistry·H P de KoningS M Jarvis
Jul 14, 1998·Molecular and Biochemical Parasitology·J I PennyS Krishna
May 10, 2000·Molecular and Biochemical Parasitology·M Ghosh, T Mukherjee
Apr 18, 2001·Molecular Pharmacology·A M SteadS A Ward
Oct 9, 2002·Nature·Malcolm J GardnerBart Barrell
Jul 2, 2003·The Journal of Biological Chemistry·Alex SteinMichael P Kavanaugh
Jul 17, 2003·International Journal for Parasitology·Harry P De KoningJonathan M Wastling
Nov 25, 2003·The Journal of Biological Chemistry·Richard J W Allen, Kiaran Kirk
May 14, 2004·The Journal of Biological Chemistry·Kshitiz ChaudharyDavid S Roos
Dec 4, 2004·The Journal of Biological Chemistry·Li-Min TingKami Kim
Jul 26, 2005·FEMS Microbiology Reviews·Harry P de KoningRichard J S Burchmore
Aug 13, 2005·Molecular Membrane Biology·Sophia GoudelaGeorge Diallinas
Aug 30, 2005·Antimicrobial Agents and Chemotherapy·Mohammed I Al-Salabi, Harry P de Koning
Jun 6, 2006·Proceedings of the National Academy of Sciences of the United States of America·Kamal El BissatiChoukri Ben Mamoun
Jun 6, 2007·Bioorganic & Medicinal Chemistry·Kathleen TooDavid Loakes

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Citations

Sep 19, 2008·The Journal of Biological Chemistry·María B CasseraVern L Schramm
Oct 30, 2008·The Journal of Biological Chemistry·Dennis C MadridKami Kim
Jun 24, 2008·Eukaryotic Cell·Megan J DownieChoukri Ben Mamoun
Jan 11, 2011·Eukaryotic Cell·Scott M Landfear
May 1, 2009·Future Medicinal Chemistry·Meryem Köse, Anke C Schiedel
Dec 19, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sarah C ZimmermannKatherine L Seley-Radtke
Apr 16, 2010·Trends in Parasitology·Henry M StainesSanjeev Krishna
Jan 23, 2010·Experimental Parasitology·Sonali MehrotraHemalatha Balaram
May 9, 2009·Trends in Parasitology·Kiaran KirkMegan J Downie
Oct 3, 2009·Molecular Microbiology·Rowena E MartinKiaran Kirk
Dec 14, 2011·Molecular Microbiology·Eva-Maria PatzewitzSylke Müller
Nov 27, 2014·Annals of the New York Academy of Sciences·I J FrameMyles H Akabas
Sep 9, 2010·Molecular Systems Biology·Germán PlataDennis Vitkup
Dec 12, 2013·The Biochemical Journal·Kiaran Kirk, Adele M Lehane
Mar 7, 2014·International Journal for Parasitology. Drugs and Drug Resistance·Dina le RouxLyn-Marie Birkholtz
Mar 8, 2020·Medicinal Research Reviews·Gustavo D Campagnaro, Harry P de Koning
May 5, 2010·The Journal of Biological Chemistry·Megan J DownieChoukri Ben Mamoun
Jan 4, 2019·Science Translational Medicine·Jerzy M DziekanPär Nordlund
May 15, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Sahil KumarRajesh K Singh
Nov 21, 2017·ACS Infectious Diseases·Gary B EvansVern L Schramm
Apr 10, 2019·Journal of Medicinal Chemistry·Thomas ChevietSuzanne Peyrottes

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