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. 2018 Jul 9;13(7):e0199574. doi: 10.1371/journal.pone.0199574

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© 2018 Oosterom et al

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Fig 1 — SAM: S-adenosylmethionine; SAH: S-adenosylhomocysteine; DHF: dihydrofolate; THF: tetrahydrofolate; TS: thymidylate synthase; DHFR: dihydrofolate reductase; MTHFD1: methylenetetrahydrofolate dehydrogenase 1; MTHFR: methylenetetrahydrofolate reductase; MTX: methotrexate. Folic acid donates a methyl-group to the one-carbon metabolism pathway. Through several steps methionine is transformed into SAM, which then donates the methyl-group for the DNA methylation process, and is transformed into SAH and homocysteine. MTX inhibits DHFR and TS. By inhibiting DHFR, MTX inhibits the pathway leading to methylation.