Editing Folate (section)

== Function ==
Tetrahydrofolate's main function in metabolism is transporting single-carbon groups (i.e., a [[methyl group]], [[methylene group]], or [[formyl group]]). These carbon groups can be transferred to other molecules as part of the modification or biosynthesis of a variety of biological molecules. Folates are essential for the synthesis of [[DNA]], the modification of DNA and [[RNA]], the synthesis of [[methionine]] from [[homocysteine]], and various other chemical reactions involved in cellular metabolism.<ref name=Naderi>{{cite journal|journal=Advances in Food and Nutrition Research |volume=83 |date=2018 |pages=195–213 |title=Chapter Five – Recent Developments in Folate Nutrition |vauthors=Naderi N, House JD |doi=10.1016/bs.afnr.2017.12.006 |pmid=29477222 |publisher=Elsevier}}</ref> These reactions are collectively known as folate-mediated one-carbon metabolism.<ref name=PKIN2020Folate /><ref name = Lan2018>{{cite journal | vauthors = Lan X, Field MS, Stover PJ | title = Cell cycle regulation of folate-mediated one-carbon metabolism | journal = Wiley Interdiscip Rev Syst Biol Med | volume = 10 | issue = 6 | pages = e1426 | date = November 2018 | pmid = 29889360 | doi = 10.1002/wsbm.1426 | s2cid = 47014043 | pmc = 11875019 }}</ref>

=== DNA synthesis ===
{{main|Purine metabolism|Pyrimidine metabolism}}
Folate derivatives participate in the biosynthesis of both purines and pyrimidines.

Formyl folate is required for two of the steps in the biosynthesis of [[inosine monophosphate]], the precursor to GMP and AMP. Methylenetetrahydrofolate donates the C1 center required for the biosynthesis of [[dTMP]] (2{{prime}}-deoxythymidine-5{{prime}}-phosphate) from [[dUMP]] (2{{prime}}-deoxyuridine-5{{prime}}-phosphate). The conversion is catalyzed by [[thymidylate synthase]].<ref name=PKIN2020Folate />

=== Vitamin B<sub>12</sub> activation ===
[[File:Folate methionine cycle.svg|thumb|class=skin-invert-image|Simplified schematic diagram of the folate methionine cycle<ref name="Froese_2019">{{cite journal | vauthors = Froese DS, Fowler B, Baumgartner MR | title = Vitamin B12, folate, and the methionine remethylation cycle-biochemistry, pathways, and regulation | journal = Journal of Inherited Metabolic Disease | volume = 42 | issue = 4 | pages = 673–685 | date = July 2019 | pmid = 30693532 | doi = 10.1002/jimd.12009 | doi-access = free }}</ref>|360px]]
Methyl-THF converts vitamin B<sub>12</sub> to methyl-B<sub>12</sub> ([[methylcobalamin]]). Methyl-B<sub>12</sub> converts homocysteine, in a reaction catalyzed by [[homocysteine methyltransferase]], to [[methionine]]. A defect in homocysteine methyltransferase or a deficiency of B<sub>12</sub> may lead to a so-called "methyl-trap" of THF, in which THF converts to methyl-THF, causing a deficiency in folate.<ref name = Hoffbrand2001/> Thus, a deficiency in B<sub>12</sub> can cause accumulation of methyl-THF, mimicking folate deficiency.