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

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Seymour KK, Yeo AE, Rieckmann KH, Christopherson RI

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

Ann Trop Med Parasitol. 1997 Sep;91(6):603-9.

PubMed ID

9425362 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Atovaquone	Dihydroorotate dehydrogenase (quinone), mitochondrial	Protein	Humans	Unknown	Inhibitor	Details