FIGURE 1.

One-carbon metabolism is required for the synthesis of purines, thymidylate (dTMP), and methionine. Mitochondrial-derived formate is a major source of 1C units and can enter the cytoplasm to function as a one-carbon unit for folate metabolism. The synthesis of dTMP occurs in the nucleus and mitochondria. At S phase, the enzymes of the thymidylate (dTMP) synthesis pathway undergo SUMO-dependent translocation to the nucleus. The remethylation of homocysteine to methionine by MTR requires vitamin B12. The one carbon is labeled in bold. The inset shows the thymidylate synthesis cycle, which involves the enzymes, SHMT1, SHMT2a, TYMS, and dihydrofolate reductase (DHFR). DHF, dihydrofolate; MTR, methionine synthase; GNMT, glycine N-methyltransferase; MTHFR, 5-methenylenetetrahydrofolate reductase.