Folate-utilizing enzymes

Folate-utilizing enzymes are a class of proteins that catalyze reactions within the one-carbon metabolism pathway, which is fundamental for the de novo synthesis of purines and thymidylate required for DNA and RNA production (StatPearls, 2023). This group includes critical therapeutic targets such as dihydrofolate reductase (DHFR), thymidylate synthase (TYMS), and glycinamide ribonucleotide transformylase (GART) (NCBI, 2022). By facilitating the transfer of one-carbon units, these enzymes support rapid cell proliferation, making them pivotal in both normal physiology and disease states like cancer. Antifolate drugs, such as methotrexate and pemetrexed, exert their effects by inhibiting these enzymes, thereby depleting the cellular pool of reduced folates and halting nucleic acid synthesis (PubMed, 2021). Beyond oncology, these enzymes are targeted to treat autoimmune conditions like rheumatoid arthritis and infectious diseases, where selective inhibition of microbial folate enzymes provides a therapeutic window (UniProt, 2023). Clinical use of these inhibitors often requires monitoring for toxicities like myelosuppression and gastrointestinal distress, sometimes managed with folate supplementation or leucovorin rescue (NIH, 2022).

Other names

Folate metabolism enzymesOne-carbon metabolism enzymesAntifolate targets

Competitive inhibition of folate-binding sites on enzymes such as dihydrofolate reductase (DHFR), thymidylate synthase (TYMS), and glycinamide ribonucleotide transformylase (GART), leading to the depletion of reduced folates and the subsequent inhibition of DNA and RNA synthesis.