Figure 2.

Synthetic pathway of folate metabolism. DHFR catalyzes the passage of a hydride from the cofactor nicotinamide adenine dinucleotide phosphate (NADPH), used as an electron donor, to dihydrofolate (DHF), through a protonation to produce tetrahydrofolate (THF). In particular, DHFR catalyzes the reduction of 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate using reduced NADPH as a cofactor [25]. Therefore, DHFR couples with thymidylate synthase (TS), which catalyzes the reductive methylation of deoxyuridine monophosphate (dUMP) in deoxythymidine monophosphate (dTMP) using N⁵-N¹⁰-methylenetetrahydrofolate (5,10-Methylene THF) as a cofactor [26].