Comparative Studies on Dihydrofolate Reductases from Plasmodium falciparum and Aotus trivirgatus*

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Abstract
Dihydrofolate reductase (EC 1.5.1.3) from the blood parasite P. falciparum and from its host, the owl monkey (A. trivirgatus), was partially purified and characterized. The MW of the parasite enzyme was estimated to be over 10 times as high as that of the host enzyme. The host enzyme had 2 pH optima whereas the parasite enzyme had only one. The activity of the host enzyme was greatly stimulated by KCl and urea, while the parasite enzyme was inhibited at high concentrations of such chaotropic agents. Km of the parasite enzyme was significantly higher than that of the host enzyme. The parasite enzyme had much lower Ki for the antifolate pyrimethamine than the host enzyme. Dihydrofolate reductases isolated from pyrimethamine-resistant and pyrimethamine-sensitive strains of P. falciparum were similar. [Because of the differences between the host and parasite enzymes, it seems possible to use antifolates such as pyrimethamine for chemotherapy.].