Folate one-carbon metabolism (FOCM) (FOCM)

Folate one-carbon metabolism (FOCM) is a fundamental metabolic network that facilitates the transfer of one-carbon units for essential cellular processes, including the synthesis of nucleotides (purines and thymidylate) and the maintenance of the methylation cycle (Ducker & Rabinowitz, 2017). This pathway is critical for DNA replication, repair, and epigenetic regulation, as it generates S-adenosylmethionine (SAM), the universal methyl donor (StatPearls, 2023). Because of its central role in cell division, FOCM is a major target in oncology, where antifolate drugs are used to inhibit enzymes like dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS) to arrest tumor growth (PubChem, 2024). Beyond cancer, disruptions in this pathway are associated with megaloblastic anemia, cardiovascular disease due to hyperhomocysteinemia, and congenital abnormalities such as neural tube defects (NIH, 2022). Therapeutic strategies often focus on modulating specific enzymes within the cycle or supplementing with folate derivatives to correct metabolic imbalances. Antifolates like methotrexate and pemetrexed are classic examples of drugs that exploit this pathway's necessity for DNA synthesis to treat malignancies and autoimmune diseases. The pathway's complexity, involving multiple enzymes and cofactors like Vitamin B12, makes it a sensitive indicator of nutritional status and a versatile therapeutic target.

Other names

One-carbon metabolismFolate cycleFolate-mediated one-carbon metabolism

Inhibition of key enzymes such as dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS) to deplete intracellular folate pools, thereby inhibiting DNA synthesis and repair.