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. 2024 Jul 2;22:146. doi: 10.1186/s12915-024-01946-6

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — Folate and folate-mediated one-carbon metabolism (OCM). a Folate comprises a pteridine ring and a p-aminobenzoic acid with polyglutamyl residues attached to the carboxyl group of the benzene ring. The one-carbon unit attached to the N5 and/or N10 positions of the pteridine ring is in the oxidation states of either formate, formaldehyde, or methanol. b Folate, through folate-mediated one-carbon metabolism (OCM), provides its one-carbon unit for purine and thymidylate biosynthesis, amino acid metabolism, S-adenosylmethionine formation, and redox homeostasis. Abbreviations: DHFR, dihydrofolate reductase; MTHFD1, methylenetetrahydrofolate dehydrogenase 1; SHMT1, cytosolic serine hydroxymethyltransferase; MTHFS, 5,10-methenyltetrahydrofolate synthetase; MTHFR, methylenetetrahydrofolate reductase; TS, thymidylate synthase; MTR, 5-methyltetrahydrofolate-homocysteine methyltransferase; MAT, methionine adenosyl transferase; MT, methyltransferase; SAHH, S-adenosylhomocysteine hydrolase; SHMT2, mitochondrial serine hydroxymethyltransferase-2; MTHFD1L, mitochondrial 10-formy-THF synthetase; MTHFD2/2L, mitochondrial bi-functional enzyme (5,10-methylene-THF dehydrogenase/5,10-methenyl-THF cyclohydrolase); MFT, mitochondrial folate transporter; RFC, reduced folate carrier; PCFT, proton-couple folate transporter; FR, folate receptor