Folate mediated one-carbon cycle. Folic acid (vitamin B9) is a cofactor in one-carbon metabolism, acting as a shuttle for methyl groups that will be used in the metabolism of s-adenosyl methionine (SAM), de novo synthesis of purines and thymidylate. Dihydrofolate reductase (dhfr), an enzyme involved in the recycling of this cofactor, reduces dihydrofolate to tetrahydrofolate (THF), thereby preparing the folate derivative for subsequent methyl group addition. This enzyme is competitively inhibited by methotrexate (MTX), a chemotherapeutic drug with a thousand fold higher binding affinity for dhfr then its natural substrate, dihydrofolate TYMS – thymidylate synthetase, MTHFD – methylenetetrahydrofolate dehydrogenase, MTHFR – methylenetetrahydrofolate reductase, MS – methionine synthase, MTRR – methionine synthase reductase, MAT- Methionine adenosyltransferase, SAHH - s-adenosyl homocysteine hydrolase, SAH – s-adenosyl homocysteine. Enzymes in red are discussed in this paper.
Lee et al. BMC Developmental Biology 2012 12:12 doi:10.1186/1471-213X-12-12