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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
ChEBI
ChEMBL
ChemSpider
MeSH
5,10-methylenetetrahydrofolate
UNII
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
O=C(O)[C@@H](NC(=O)c1ccc(cc1)N4CC3N(C=2C(=O)/N=C(/N)NC=2NC3)C4)CCC(=O)O
Properties
C20 H23 N7 O6
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).
Chemical compound
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 CH2 2+ 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.
MTHFR metabolism: folate cycle, methionine cycle, trans-sulfuration and
hyperhomocysteinemia .
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.
See also
References
^
"Entrez Gene: MTHFR methylenetetrahydrofolate reductase (NAD(P)H)" .
^ Födinger M, Hörl WH, Sunder-Plassmann G (2000). "Molecular biology of 5,10-methylenetetrahydrofolate reductase". J Nephrol . 13 (1): 20–33.
PMID
10720211 .
^ Marx, C. J.; Chistoserdova, L.; Lidstrom, M. E. (2003).
"Formaldehyde-detoxifying role of the tetrahydromethanopterin-linked pathway in Methylobacterium extorquens AM1" . J. Bacteriol . 185 (24): 7160–8.
doi :
10.1128/jb.185.23.7160-7168.2003 .
PMC
296243 .
PMID
14645276 .
^ Danenberg, Peter V.; Gustavsson, Bengt; Johnston, Patrick; Lindberg, Per; Moser, Rudolf; Odin, Elisabeth; Peters, Godefridus J.; Petrelli, Nicholas (2016-10-01).
"Folates as adjuvants to anticancer agents: Chemical rationale and mechanism of action" . Critical Reviews in Oncology/Hematology . 106 : 118–131.
doi :
10.1016/j.critrevonc.2016.08.001 .
ISSN
1879-0461 .
PMID
27637357 .
Fat soluble
Water soluble
Combinations