DHF is an important intermediate in de novo synthesis of dTTP. DHF is produced from 5,10-methylene THF in the conversion of dUMP to dTMP catalyzed by thymidylate synthase (Figure 22.18). Subsequently, 5,10-methylene-THF must be regenerated from DHF (catalyzed by dihydrofolate reductase) in order for de novo dTMP synthesis to occur. Inhibitors of dihydrofolate reductase, such as methotrexate and trimethoprim, ultimately inhibit de novo production of dTTP.

See also: De Novo Biosynthesis of Purine Nucleotides, Tetrahydrofolate Coenzymes