5,10-Methylenetetrahydrofolate

Names
IUPAC name N-[4-(3-amino-1-oxo-1,4,5,6,6a,7-hexahydroimidazo[1,5-f]pteridin-8(9H)-yl)benzoyl]-L-glutamic acid
Other names 5,10-CH2-THF, MTHF
Identifiers
CAS Number	3432-99-3 Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:20502 Y
ChEMBL	ChEMBL117348 Y
ChemSpider	97272 Y
MeSH	5,10-methylenetetrahydrofolate
PubChem CID	108194
UNII	0SXY5ET48B Y
CompTox Dashboard (EPA)	DTXSID90955873
InChI InChI=1S/C20H23N7O6/c21-20-24-16-15(18(31)25-20)27-9-26(8-12(27)7-22-16)11-3-1-10(2-4-11)17(30)23-13(19(32)33)5-6-14(28)29/h1-4,12-13H,5-9H2,(H,23,30)(H,28,29)(H,32,33)(H4,21,22,24,25,31)/t12?,13-/m0/s1 Y Key: QYNUQALWYRSVHF-ABLWVSNPSA-N Y InChI=1/C20H23N7O6/c21-20-24-16-15(18(31)25-20)27-9-26(8-12(27)7-22-16)11-3-1-10(2-4-11)17(30)23-13(19(32)33)5-6-14(28)29/h1-4,12-13H,5-9H2,(H,23,30)(H,28,29)(H,32,33)(H4,21,22,24,25,31)/t12?,13-/m0/s1 Key: QYNUQALWYRSVHF-ABLWVSNPBB
SMILES O=C(O)[C@@H](NC(=O)c1ccc(cc1)N4CC3N(C=2C(=O)/N=C(/N)NC=2NC3)C4)CCC(=O)O
Properties
Chemical formula	C20H23N7O6
Molar mass	457.44 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

5,10-Methylenetetrahydrofolate (N5,N10-Methylenetetrahydrofolate; 5,10-CH₂-THF) is cofactor in several biochemical reactions. It exists in nature as the diastereoisomer [6R]-5,10-methylene-THF.

As an intermediate in one-carbon metabolism, 5,10-CH₂-THF converts to 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, and methenyltetrahydrofolate. It is substrate for the enzyme methylenetetrahydrofolate reductase (MTHFR)^[1][2] It is mainly produced by the reaction of tetrahydrofolate with serine, catalyzed by the enzyme serine hydroxymethyltransferase.

Selected functions

Formaldehyde equivalent

Methylenetetrahydrofolate is a source of the equivalent of formaldehyde or CH₂²⁺ in biosyntheses.

Methylenetetrahydrofolate is also an intermediate in the detoxification of formaldehyde.^[3]

Pyrimidine biosynthesis

It is the one-carbon donor for thymidylate synthase, for methylation of 2-deoxy-uridine-5-monophosphate (dUMP) to 2-deoxy-thymidine-5-monophosphate (dTMP). The coenzyme is necessary for the biosynthesis of thymidine and is the C1-donor in the reactions catalyzed by TS and thymidylate synthase (FAD).

Biomodulator

[6R]-5,10-methylene-THF is a biomodulator that has proven to enhance the desired cytotoxic antitumor effect of Fluorouracil (5-FU) and can bypass the metabolic pathway required by other folates (such as leucovorin) to achieve necessary activation.^[4] The active metabolite is being evaluated in clinical trials for patients with colorectal cancer in combination with 5-FU.