Figure 1.

Folate one-carbon metabolism. One carbon metabolism enzymes are presented and activated in three different compartments, the nucleus, cytosol, and mitochondria. The flow of permeable metabolites linked the reactions between these compartments, such as formate, serine, and glycine. Briefly, different forms of THFs, function as carriers, transfer one-carbon units as from serine to formate in the mitochondria. Formate then supply the biosynthesis of purine in the cytosol and thymidylate in the nucleus. The reactions in mitochondria are catalyzed mainly by SHMT2, MTHFD2, and MTHFD1L; while in cytosol and nucleus are by SHMT1/2 and MTHFD1. The enzymatic functions of MTHFD2 in the mitochondria are well-studied, while its role in the nucleus is largely unknown and may hold various non-metabolic functions.