:5,10-Methylenetetrahydrofolate
{{distinguish|5,10-Methenyltetrahydrofolate}}
{{chembox
| Verifiedfields = changed
| verifiedrevid = 477223777
| ImageFile=5,10-methylenetetrahydrofolic acid.svg
| ImageClass = skin-invert-image
| ImageSize=
| IUPACName= N-[4-(3-amino-1-oxo-1,4,5,6,6a,7-hexahydroimidazo[1,5-f]pteridin-8(9H)-yl)benzoyl]-L-glutamic acid
| OtherNames=5,10-CH2-THF,
MTHF
|Section1={{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 97272
| 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
| InChIKey = QYNUQALWYRSVHF-ABLWVSNPBB
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 117348
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = QYNUQALWYRSVHF-ABLWVSNPSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo=3432-99-3
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 0SXY5ET48B
| PubChem=108194
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 20502
| SMILES = O=C(O)[C@@H](NC(=O)c1ccc(cc1)N4CC3N(C=2C(=O)/N=C(/N)NC=2NC3)C4)CCC(=O)O
| MeSHName=5,10-methylenetetrahydrofolate
}}
|Section2={{Chembox Properties
| Formula=C20H23N7O6
| MolarMass=457.44 g/mol
| Appearance=
| Density=
| MeltingPt=
| BoilingPt=
| Solubility=
}}
|Section3={{Chembox Hazards
| MainHazards=
| FlashPt=
| AutoignitionPt =
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}}
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), which gives 5-methyltetrahydrofolate.{{cite web | title = Entrez Gene: MTHFR methylenetetrahydrofolate reductase (NAD(P)H)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4524}}{{cite journal| vauthors=Födinger M, Hörl WH, Sunder-Plassmann G| title=Molecular biology of 5,10-methylenetetrahydrofolate reductase. | journal=J Nephrol | year= 2000 | volume= 13 | issue= 1 | pages= 20–33 | pmid=10720211 }} 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.{{cite journal|author1=Marx, C. J. |author2=Chistoserdova, L. |author3=Lidstrom, M. E.|year=2003|title=Formaldehyde-detoxifying role of the tetrahydromethanopterin-linked pathway in Methylobacterium extorquens AM1|journal=J. Bacteriol.|volume=185|issue=24|pages=7160–8|pmid=14645276|pmc=296243|doi=10.1128/jb.185.23.7160-7168.2003}}
=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.{{Cite journal|last1=Danenberg|first1=Peter V.|last2=Gustavsson|first2=Bengt|last3=Johnston|first3=Patrick|last4=Lindberg|first4=Per|last5=Moser|first5=Rudolf|last6=Odin|first6=Elisabeth|last7=Peters|first7=Godefridus J.|last8=Petrelli|first8=Nicholas|date=2016-10-01|title=Folates as adjuvants to anticancer agents: Chemical rationale and mechanism of action|journal=Critical Reviews in Oncology/Hematology|volume=106|pages=118–131|doi=10.1016/j.critrevonc.2016.08.001|issn=1879-0461|pmid=27637357|doi-access=free}} The active metabolite is being evaluated in clinical trials for patients with colorectal cancer in combination with 5-FU.
File:MTHFR metabolism.svg. 5-MTHF: 5-methyltetrahydrofolate; 5,10-methylenetetrahydrofolate; BAX: Bcl-2-associated X protein; BHMT: betaine-homocysteine S-methyltransferase; CBS: cystathionine beta synthase; CGL: cystathionine gamma-lyase; DHF: dihydrofolate (vitamin B9); DMG: dimethylglycine; dTMP: thymidine monophosphate; dUMP: deoxyuridine monophosphate; FAD+ flavine adenine dicucleotide; FTHF: 10-formyltetrahydrofolate; MS: methionine synthase; MTHFR: methylenetetrahydrofolate reductase; SAH: S-adenosyl-L-homocysteine; SAME: S-adenosyl-L-methionine; THF: tetrahydrofolate.]]
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See also
References
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{{Enzyme cofactors}}
{{Vitamin}}
{{DEFAULTSORT:Methylenetetrahydrofolate, 5, 10-}}