Stored plasma samples collected after diagnosis were analyzed for total folate (the sum of all folate vitamers), and the vitamers folic acid, tetrahydrofolic acid
(THF), 5-methyl tetrahydrofolic acid
, and 5-formylTHF/MeFox.
Pyrimethamine's mechanism of action is through inhibition of parasitic dihydrofolate reductase resulting in inhibition of vital tetrahydrofolic acid
The basic principle of its therapeutic efficacy is related to the inhibition of dihydrofolate reductase, a key enzyme in the folic acid metabolism, which converts dihydrofolicacid to tetrahydrofolic acid
. The perturbation in the folic acid metabolism leads to depletion of nucleotide precursors like thymidylates and purines, which in turn inhibits DNA, RNA and protein synthesis (16, 17).
FA enters the monocarbon (C1) pool of cellular metabolism via binding to tetrahydrofolic acid
; as such, it can participate in the structure of macromolecules, such as nucleic acids.