Folate-mediated one-carbon metabolism

Folate-mediated one-carbon metabolism. Folate-mediated one-carbon metabolism is required for the de novo synthesis of purines and thymidylate and for the remethylation of homocysteine to methionine. Mitochondrial-derived formate can enter the cytoplasm and function as a one-carbon donor through the conversion of THF to 10-formyl-THF. 5,10-Methylene-THF, which can be generated through the reduction of 10-formyl-THF or through the catalytic activity of SHMT1, provides the one-carbon units for the TS-catalyzed conversion of dUMP to thymidylate. It also serves as a substrate for methylene-THF reductase (MTHFR), which reduces 5,10-methylene-THF to ultimately form S-adenosylmethionine (AdoMet), the one-carbon donor in numerous cellular methylation reactions. De novo thymidylate biosynthesis also occurs in the nucleus through the SUMO-dependent import of the thymidylate synthesis pathway during S-phase. Hcy, homocysteine; DHF, dihydrofolate.

Publication

A UV-responsive Internal Ribosome Entry Site Enhances Serine Hydroxymethyltransferase 1 Expression for DNA Damage Repair. (2009) Jennifer T. Fox, et al. J Biol Chem. 2009 Nov 6;284(45):31097-31108. Figure: F1. Homo sapiens

Disease mentions