Plasmodia biochemical pathway

Oakley, M. S., Kumar, S., Anantharaman, V., Zheng, H., Mahajan, B., Haynes, J. D., Moch, J. K., Fairhurst, R., McCutchan, T. F., and Aravind, L. (2007). Molecular factors and biochemical pathways induced by febrile temperature in intraerythrocytic Plasmodium falciparum parasites. Infect. Immun. 75, 2012-2025. 

In 1968, my graduate student Charles Walsh and I addressed the following question What are the pyrimidine sources for nucleic acid synthesis by Plasmodium lophurae We found the parasite synthesized pyrimidines de novo (Walsh and Sherman, 1968b). The evidence for a de novo synthesis was the presence of the key enzymes, thymidylate synthetase and oroti-dine-5-monophosphate pyrophosphorylase, as well as the demonstration of the incorporation of 14C-bicarbonate into cytosine, uracil and thymine. Finding a de novo pathway for the synthesis of pyrimidines by the malaria parasite would, in the next three decades, provide a biochemical basis for the mechanism of action of anti-folate anti-malarials as well as contributing to an understanding of the unique properties of the malaria parasite mitochondrion. 

Ginsburg, H., Krugliak, M., Eidelman, O., and Cabantchik, Z. I. (1983). New permeability pathways induced in membranes of Plasmodium falciparum infected erythrocytes. Mol. Biochem. Parasitol. 8,177-190. 

Jin X, Jin HR, Lee D, Lee JH, Kim SK, Lee JJ (2008) A quassinoid 6alpha-tigloyloxycha-parrinone inhibits hypoxia-inducible factor-1 pathway by inhibition of eukaryotic translation initiation factor 4E phosphorylation. European J Pharmacol 592 41 Kirby GC, O Neill MJ, Phillipson JD, Warhurst DC (1989) hi vitro studies on the mode of action of quassinoids with activity against chloroquine-resistant Plasmodium falciparum. Biochem Pharmacol 38 4367... 

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