Figure 1.

Simplified chart of the one-carbon metabolism. In the methionine cycle, methionine is converted into SAM via MAT. SAM is a universal methyl donor. SAM is converted to SAH in transmethylation reactions by methyltransferases. The resulting SAH is converted to homocysteine, which can either pass through the transsulfuration pathway, forming cystein in 2 steps catalyzed by CBS and CSE, or remethylated to methionine by MS, using the methyl group provided by Met-THF. The remethylation regenerates THF, which is then used to produce methylene-THF and Met-THF via SHMT1 and MTHFR, respectively. Methylene-THF can also be generated in the mitochondria by pathways that involve SHMT2 and GLDC. In the methionine salvage pathway, SAM decarboxylation produces an aminopropyl group donor for Putr and Spd synthesis. The donation of the aminopropyl group is catalyzed by aminopropyl transferases and produces MTA. MTA is converted back to SAM via MTAP. Abbreviations: AHCY, adenosylhomocysteinase; CBS, cystathionine beta synthase; CO2, carbon dioxide; CSE, cystathionine γ-lyase; Cys, cysteine; dcSAM, decarboxylated S-adenosylmethionine; GLDC, glycine decarboxylase; Gly, glycine; Hcy, homocysteine; MAT, methionine adenosyltransferase; methylene-THF, methylenetetrahydrofolate; Met-THF, methyltetrahydrofolate; MTA, methylthioadenosine; MTAP, methylthioadenosine phosphorylase; MTHFR, methylenetetrahydrofolate reductase; MTR, methionine synthase; MTs, methyltransferases; NH3, ammonia; Putr, putrescine; SAH, S-adenosylhomocysteine; SAM, S-adenosylmethionine; Ser, serine; SHMT1, serine hydroxymethyltransferase 1; SHMT2, serine hydroxymethyltransferase 2; SMS, spermine synthase; Spd, spermidine; Spm, spermine; SRM, spermidine synthase;; THF, tetrahydrofolate.