Folate and homocysteine metabolism enzymes

Folate and homocysteine metabolism enzymes constitute a vital biochemical network responsible for one-carbon metabolism, which is fundamental to DNA synthesis, repair, and epigenetic regulation [1, 2]. This group includes key enzymes such as dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and thymidylate synthase (TYMS) [1, 5]. These enzymes work in concert to provide the methyl groups necessary for the conversion of homocysteine to methionine and the production of nucleotides like thymidine and purines [1, 2]. Disruptions in this pathway, often due to genetic polymorphisms or nutritional deficiencies, can lead to elevated homocysteine levels, which are associated with an increased risk of cardiovascular disease, stroke, and neural tube defects [1, 5]. In oncology, these enzymes are primary targets for antimetabolite drugs, such as methotrexate and 5-fluorouracil, which inhibit DNA replication to arrest tumor growth [3, 4]. Furthermore, the pathway is modulated through supplementation with folic acid and B vitamins to mitigate metabolic imbalances and reduce disease risk [2, 5].

Other names

One-carbon metabolism enzymesFolate cycle enzymesHomocysteine pathway enzymesMethionine cycle enzymesFolate-mediated one-carbon metabolism (FOCM) enzymes

Inhibition of dihydrofolate reductase (DHFR), inhibition of thymidylate synthase (TYMS), and supplementation of pathway cofactors (folate, B12, B6) to reduce homocysteine levels.