Abstract
Purine uptake has been studied in many protozoan parasites in the last few years, and several of the purine transporters have been cloned. In contrast, very little is known about the salvage of preformed pyrimidines by protozoa, and no pyrimidine transporters have been cloned, yet chemotherapy based on pyrimidine nucleobases and nucleosides has been as effective as purine antimetabolites in the treatment of infectious and neoplastic disease. Here, we surveyed the presence of pyrimidine transporters in Trypanosoma brucei brucei. We could not detect any mediated uptake of thymine, thymidine or cytidine, but identified a very high-affinity transporter for cytosine, designated C1, with a K(m) value of 0.048+/-0.009 microM. We also confirmed the presence of the previously reported U1 uracil transporter and found it capable of mediating uridine uptake as well, with a K(m) of 33+/-5 microM. A higher-affinity U2 uridine transporter (K(m)=4.1+/-2.1 microM) was also identified, but efficiency of the C1 and U2-mediated transport was low. Pyrimidine antimetabolites were tested as potential trypanocidal agents and only 5-fluorouracil was found to be effective. This drug was efficiently taken up by bloodstream forms of T. b. brucei.
References
Aug 24, 1992·Biochimica Et Biophysica Acta·R A DaveyP L Ey
Aug 24, 1992·Biochimica Et Biophysica Acta·P L EyG A Duffield
Oct 1, 1991·Molecular and Biochemical Parasitology·R A DaveyG Mayrhofer
Sep 17, 1982·Biochimica Et Biophysica Acta·D J Hammond, W E Gutteridge
Jan 14, 1993·Nature·N S Carter, A H Fairlamb
Aug 1, 1997·European Journal of Biochemistry·H P de Koning, S M Jarvis
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
Aug 26, 1998·Proceedings of the National Academy of Sciences of the United States of America·G VasudevanS M Landfear
Jun 3, 1999·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·H P de Koning, S M Jarvis
Apr 1, 2000·Molecular and Biochemical Parasitology·H P de KoningS M Jarvis
May 10, 2000·Molecular and Biochemical Parasitology·M Ghosh, T Mukherjee
May 4, 2001·International Journal for Parasitology·H P de Koning
Jun 19, 2001·Journal of Medicinal Chemistry·J C BressiM H Gelb
Nov 14, 2001·The Journal of Biological Chemistry·Gregory A KicskaKami Kim
May 11, 2002·The Journal of Biological Chemistry·Lynsey J M WallaceHarry P De Koning
Jul 18, 2002·International Journal of Dermatology·Ali Z MomeniMalihalsadat Aminjavaheri
Apr 23, 2003·The Journal of Biological Chemistry·Richard J S BurchmoreHarry P de Koning
Jul 17, 2003·International Journal for Parasitology·Harry P De KoningJonathan M Wastling
Sep 3, 2003·Pharmacology & Therapeutics·Mahmoud H el Kouni
Dec 4, 2003·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Pascal MäserRonald Kaminsky
Oct 14, 2004·Molecular and Biochemical Parasitology·Marco A SanchezScott M Landfear
Dec 2, 2004·Nucleosides, Nucleotides & Nucleic Acids·L J M WallaceH P de Koning
Feb 3, 2005·Experimental Parasitology·Manal J NattoHarry P de Koning
Mar 31, 2005·Parasitology·I G PapageorgiouH P De Koning
Jul 26, 2005·FEMS Microbiology Reviews·Harry P de KoningRichard J S Burchmore
Oct 27, 2005·Bioorganic & Medicinal Chemistry·Boris RodenkoGerrit-Jan Koomen
Citations
Mar 24, 2012·The Journal of Biological Chemistry·Farahnaz RanjbarianAnders Hofer
Mar 26, 2011·Molecular Pharmacology·Ibrahim A TekaHarry P de Koning
Nov 28, 2013·PLoS Neglected Tropical Diseases·Jean-François RittMarc Ouellette
Mar 19, 2013·PloS One·Juma A M AliHarry P de Koning
May 1, 2009·Future Medicinal Chemistry·Meryem Köse, Anke C Schiedel
Dec 1, 2009·Experimental Parasitology·Jana M SimmonsRobert P Hausinger
Jul 29, 2008·The International Journal of Biochemistry & Cell Biology·Víctor M Castillo-AcostaDolores González-Pacanowska
Mar 22, 2007·Trends in Parasitology·Vivian Bellofatto
Dec 21, 2007·Proteomics·Daniel J BridgesRichard J S Burchmore
Mar 4, 2008·Molecular Microbiology·Tracy L ArakakiEthan A Merritt
Aug 29, 2013·Molecular Microbiology·Han B OngAlan H Fairlamb
Oct 23, 2015·Metabolomics : Official Journal of the Metabolomic Society·Dong-Hyun KimMichael P Barrett
Dec 4, 2012·Molecular and Biochemical Parasitology·Víctor M Castillo-AcostaDolores González-Pacanowska
Jan 15, 2010·Journal of Molecular Biology·Eric T LarsonEthan A Merritt
Nov 27, 2007·International Journal for Parasitology·I PapageorgiouG Diallinas
Jan 16, 2016·PloS One·Vishal NanavatyBin Su
Jan 22, 2019·ChemMedChem·Michela CeroneMaria Laura Bolognesi
Feb 10, 2018·Parasites & Vectors·Kartikeya Tiwari, Vikash Kumar Dubey
Mar 17, 2018·Scientific Reports·Godwin U EbilomaHarry P De Koning
Nov 29, 2012·Molecular Pharmacology·Juma A M AliHarry P De Koning
Jul 31, 2020·PLoS Neglected Tropical Diseases·Jane C MundayHarry P de Koning
Mar 8, 2020·Medicinal Research Reviews·Gustavo D Campagnaro, Harry P de Koning
Dec 21, 2014·Molecular Pharmacology·Abdulsalam A M AlkhaldiHarry P de Koning
Aug 8, 2019·Scientific Reports·Abdullah AlotaibiDavid G Watson
Aug 16, 2016·PLoS Neglected Tropical Diseases·Anthonius A EzeHarry P De Koning
Jan 9, 2021·ACS Infectious Diseases·Miriam Yagüe-CapillaDolores González-Pacanowska
Jul 27, 2021·PLoS Pathogens·Pieter C SteketeeLiam J Morrison
Nov 6, 2021·Molecular Microbiology·Manal J NattoHarry P De Koning