Human folate pathway enzymes

The human folate pathway enzymes represent a group of essential proteins involved in the folate cycle and one-carbon metabolism, which are critical for the biosynthesis of nucleotides and amino acids [1.1.1, 1.3.1]. Key enzymes in this pathway include dihydrofolate reductase (DHFR), thymidylate synthase (TYMS), and methylenetetrahydrofolate reductase (MTHFR), which facilitate the transfer of one-carbon units for DNA synthesis and repair [1.1.3, 1.2.2]. These enzymes are major therapeutic targets in the treatment of various cancers and autoimmune diseases, such as rheumatoid arthritis, where antifolate drugs are employed to inhibit cell proliferation [1.2.1, 1.3.4]. For instance, methotrexate and pemetrexed directly inhibit DHFR and other folate-dependent enzymes to deplete the pool of reduced folates necessary for thymidylate and purine production [1.1.1, 1.2.3]. Additionally, the pathway plays a vital role in maintaining homocysteine levels and supporting cellular methylation reactions [1.3.1, 1.3.2]. Genetic polymorphisms in these enzymes, particularly MTHFR, are significant clinical biomarkers that influence drug efficacy, toxicity, and the risk of developmental disorders like neural tube defects [1.1.3, 1.2.5].

Other names

Folate metabolism enzymesOne-carbon metabolism enzymesFolate cycle enzymesFolate-dependent enzymes

Inhibition of folate-dependent enzymes leading to the depletion of nucleotide precursors and disruption of DNA synthesis and repair [1.1.1, 1.2.3].