DIHYDROFOLATE REDUCTASES WITHIN GENUS TRYPANOSOMA

Dihydrofolate reductase activity was detected in extracts of rat-adapted bloodstream forms of Trypanosoma (Trypanozoon) brucei, T. (T.)rhodesiense, T. (T.)equiperdum, T.(Duttonella)vivax, T.(Nannomonas) congolense (section Salivaria); T.(Herpetosoma)lewisi, and T.(Schizotrypanum)cruzi (section Stercoraria). This enzyme was also detected in extracts of culture forms of T.(T.)rhodesiense, T.(H.)lewisi, and T.(S.)cruzi. The trypanosomal dihydrofolate reductases shared the general properties of the analogous enzyme from diverse genera in their requirement for dihydrofolic acid as substrate and reduced nicotinamide adenine dinucleotide phosphate as cofactor. They also showed the characteristic extreme sensitivity to the inhibitory action of 4-amino analogs of folic acid such as methotrexate. On the other hand, the trypanosomal reductases exhibited a pattern of susceptibility to inhibition by certain 2,4-diaminopyrimidines and related heterocyclic compounds which was different from the patterns of susceptibility to these agents that have been described for reductases from bacterial and mammalian sources. Superimposed upon this distinctive pattern, moreover, was a further differential response, whereby the drug sensitivities of the reductases of salivarian trypanosomes were almost identical and, as a group, clearly distinguishable from those of the stercorarian species. Those properties of dihydrofolate reductases from culture and bloodstream forms of T.(T.)rhodesiense, T.(H.) lewisi, or T.(S.)cruzi that were compared were closely similar. © 1969.