5,6,7,8-Tetrahydrofolate (THF)

THF is a folate derivate with a role in de novo synthesis of purines (Figure 22.4) and dTMP (Figure 22.18)

Dihydrofolate reductase catalyzes the conversion of dihydrofolate (DHF) to THF. This reaction is essential for the recycling of DHF to 5,10-methylenetetrahydrofolate for use by thymidylate synthase in de novo synthesis of dTMP. Inhibitors of dihydrofolate reductase, such as methotrexate and trimethoprim, ultimately inhibit production of dTTP.

THF and 5,10-methylenetetrahydrofolate can also be interconverted by the glycine catabolic reaction below

Glycine + THF + NAD⁺ -> 5,10-Methylenetetrahydrofolate + CO2 + NH3 + NADH + H⁺

See also: De Novo Biosynthesis of Purine Nucleotides, DHF, N-10-Formyltetrahydrofolate, 5,10-Methylenetetrahydrofolate