Folate-Mediated One-Carbon Metabolism. One-carbon metabolism is required for the de novo synthesis of purines and thymidylate, and for the remethylation of homocysteine to methionine. The de novo thymidylate pathway is SUMOylated and translocates to the nucleus during S-phase. Mitochondria generate formate from the amino acids serine and glycine. THF, tetrahydrofolate; AdoMet, S-adenosylmethionine; MTHFD, Methylenetetrahydrofolate Dehydrogenase; MTR, Methionine Synthase; MTHFR, Methylenetetrahydrofolate Reductase; SHMT1, Cytoplasmic Serine Hydroxymethyltransferase; SHMT2α, Serine Hydroxymethyltransferase 2α TYMS, Thymidylate Synthase; DHFR, Dihydrofolate Reductase; GSC, Glycine Cleavage System.