Folate-metabolizing enzymes

Folate-metabolizing enzymes are a group of essential proteins that facilitate one-carbon transfer reactions, which are vital for the de novo synthesis of purines and thymidylate, the building blocks of DNA (StatPearls, 2023). This group includes key therapeutic targets such as dihydrofolate reductase (DHFR), thymidylate synthase (TYMS), and various formyltransferases (UniProt, 2024). By managing the intracellular pool of reduced folates, these enzymes support rapid cell division and DNA repair, making them critical in both normal physiology and the progression of various cancers (PubMed, PMID: 23534378). Antifolate drugs, such as methotrexate and pemetrexed, target these enzymes to induce nucleotide deficiency and inhibit tumor growth (PubChem, 2024). Additionally, differences in folate metabolism between humans and pathogens allow these enzymes to be exploited as targets for antibacterial and antiprotozoal therapies (NIH, 2023).

Other names

Folate-binding enzymesFolate-dependent enzymesOne-carbon metabolism enzymesAntifolate targets

Competitive inhibition of folate-dependent enzymes, leading to the depletion of tetrahydrofolate pools and subsequent inhibition of purine and pyrimidine biosynthesis (StatPearls, 2023; PubChem, 2024).