Folate-mediated 1-carbon metabolism

Folate-mediated 1-carbon metabolism. Folate-activated 1-carbons are utilized in the synthesis of purines and thymidylate (dTMP) and in the methylation of homocysteine to methionine. Methionine can be converted to a methyl donor through its adenosylation to S-adenosylmethionine (AdoMet). Mitochondrial-derived formate traverses to the cytoplasm, where it is incorporated into the folate-activated 1-carbon pool. Nuclear folate metabolism occurs through the SUMO-dependent import of the de novo thymidylate synthase pathway from the cytoplasm to the nucleus (,). SHMT isozymes are present in each of these 3 compartments and function to generate single carbons from the hydroxymethyl group of serine in the form of 5,10-methylene-THF. The 1-carbon unit is labeled in bold. MTHFD1, methylenetetrahydrofolate dehydrogenase; MTR, methionine synthase; MTHFR, methylenetetrahydrofolate reductase; SHMT1, cytoplasmic serine hydroxymethyltransferase; TYMS, thymidylate synthase; DHFR, dihydrofolate reductase.

Publication

One-Carbon Metabolism–Genome Interactions in Folate-Associated Pathologies. (2009) Patrick J. Stover. J Nutr. 2009 Dec;139(12):2402-2405. Figure: F1. All organisms Mus musculus Homo sapiens Drosophila melanogaster

Disease mentions