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Folate Cofactor Biosynthesis by Plasmodium berghei. Comparison of Folate and Dihydrofolate as Substrates*
Authors:ROBERT FERONE  GEORGE H HITCHINGS
Abstract:SYNOPSIS. The ability of Plasmodium berghei to convert folate and dihydrofolate to folinate in vitro was investigated. Neither parasitized mouse erythrocytes nor free parasites synthesized more than trace amounts of folinate from folate under a wide variety of experimental conditions. Since disrupted cell preparations were no more efficient than whole cells, permeability barriers did not seem to be involved. However, dihydrofolate was a good substrate for the synthesis of folinate by uninfected and parasitized erythrocytes, and by free parasites. The reaction by parasitized erythrocytes required NADPH and dihydrofolate, and was inhibited by pyrimethamine, indicating the presence of dihydrofolate reductase in P. bergkei. It was postulated that P. berghei cannot utilize folate directly, since these experiments indicate that the cells lack a folate reductase. This finding is consistent with the hypothesis that plasmodia synthesize folate cofactors de novo, and do not utilize exogenous folates.
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