PMID: 9425362Jan 13, 1998Paper

dCTP levels are maintained in Plasmodium falciparum subjected to pyrimidine deficiency or excess

Annals of Tropical Medicine and Parasitology
K K SeymourR I Christopherson

Abstract

The pyrimidine antagonists, 6-L-thiodihydroorotate (TDHO) and atovaquone, are known to induce inhibition of de-novo pyrimidine biosynthesis in Plasmodium falciparum growing in erythrocytic culture, at reactions catalysed by dihydroorotase and dihydroorotate dehydrogenase, respectively. In the present study, TDHO and atovaquone induced decreases in the levels of UTP, CTP and dTTP but not dCTP in P. falciparum. Addition of orotate with either antagonist increased UTP, CTP and dTTP but depressed GTP, ATP, dATP and dCTP, suggesting that these drugs indirectly modulate the activity of ribonucleotide reductase. The changes induced in the levels of dNTP by these pyrimidine antagonists are similar to those previously described for the antifolates, cycloguanil and WR99210.

Citations

Dec 2, 2004·Nucleosides, Nucleotides & Nucleic Acids·R I ChristophersonR I Menz
Sep 3, 2010·BMC Systems Biology·Carola HuthmacherHermann-Georg Holzhütter
May 9, 2012·Proceedings of the National Academy of Sciences of the United States of America·Giancarlo A BiaginiStephen A Ward
Jan 8, 2013·The Journal of Antimicrobial Chemotherapy·Gemma L NixonGiancarlo A Biagini

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