Record Information
Version2.0
Creation Date2012-05-31 13:50:44 -0600
Update Date2015-09-17 15:41:12 -0600
Secondary Accession Numbers
  • ECMDB01354
Identification
Name:5,10-Methylene-THF
Description:5,10-Methylene-THF is an intermediate in the metabolism of methane and the metabolism of nitrogen. 5,10-Methylenetetrahydrofolate (5,10-CH2-THF) is the substrate used by the enzyme methylenetetrahydrofolate reductase (MTHFR) to generate 5-methyltetrahydrofolate (5-MTHF, or levomefolic acid). 5,10-CH2-THF can also be used as a coenzyme in the biosynthesis of thymidine. More specifically it is the C1-donor in the reactions catalyzed by thymidylate synthase and thymidylate synthase (FAD). It also acts as a coenzyme in the synthesis of serine from glycine via the enzyme serine hydroxymethyl transferase. Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine.
Structure
Thumb
Synonyms:
  • (6R)-5,10-methylenetetrahydrofolate
  • (6R)-5,10-methylenetetrahydrofolic acid
  • 5,10-Methenyltetrahydropteroylglutamate
  • 5,10-Methenyltetrahydropteroylglutamic acid
  • 5,10-Methylene-6-Hydrofolate
  • 5,10-Methylene-6-Hydrofolic acid
  • 5,10-Methylene-THF
  • 5,10-Methylenetetrahydrofolate
  • 5,10-Methylenetetrahydrofolic acid
  • 5,10-Methylenetetrahydropteroyl mono-L-glutamate
  • 5,10-Methylenetetrahydropteroyl mono-L-glutamic acid
  • 5,10MeL-THF
  • N5,N10-methylenetetrahydrofolate
  • N5,N10-methylenetetrahydrofolic acid
  • N5>,N10-methylenetetrahydrofolate
  • N5>,N10-methylenetetrahydrofolic acid
  • N5,N10-methylenetetrahydrofolate
Chemical Formula:C20H23N7O6
Weight:Average: 457.4399
Monoisotopic: 457.170981503
InChI Key:QYNUQALWYRSVHF-PZORYLMUSA-N
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?/m1/s1
CAS number:31690-11-6
IUPAC Name:(2S)-2-({4-[(6aR)-3-amino-1-oxo-1H,2H,5H,6H,6aH,7H,8H,9H-imidazolidino[1,5-f]pteridin-8-yl]phenyl}formamido)pentanedioic acid
Traditional IUPAC Name:5,10-Methylene-THF
SMILES:[H][C@@]12CN(CN1C1=C(NC2)N=C(N)NC1=O)C1=CC=C(C=C1)C(=O)NC(CCC(O)=O)C(O)=O
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as hippuric acids. These are compounds containing hippuric acid, which consists of a of a benzoyl group linked to the N-terminal of a glycine.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzamides
Direct ParentHippuric acids
Alternative Parents
Substituents
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • Hippuric acid
  • Pterin
  • Phenylimidazolidine
  • Pteridine
  • Aminobenzoic acid or derivatives
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Imidazopyrazine
  • Benzoic acid or derivatives
  • Aminobenzamide
  • Dialkylarylamine
  • Benzoyl
  • Hydroxypyrimidine
  • Secondary aliphatic/aromatic amine
  • Amino fatty acid
  • Fatty acyl
  • Pyrimidine
  • Dicarboxylic acid or derivatives
  • Heteroaromatic compound
  • Imidazolidine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Secondary amine
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Physical Properties
State:Solid
Charge:-2
Melting point:Not Available
Experimental Properties:
PropertyValueSource
Predicted Properties
PropertyValueSource
Water Solubility0.82 g/LALOGPS
logP-0.94ALOGPS
logP-2ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)2.93ChemAxon
pKa (Strongest Basic)4.6ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area189.69 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity123.96 m³·mol⁻¹ChemAxon
Polarizability45.76 ųChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Biological Properties
Cellular Locations:Cytoplasm
Reactions:
Glycine + NAD + Tetrahydrofolic acid > Carbon dioxide + 5,10-Methylene-THF + NADH + Ammonium
alpha-Ketoisovaleric acid + Water + 5,10-Methylene-THF + a-Ketoisovaleric acid <> 2-Dehydropantoate + Tetrahydrofolic acid
5,10-Methylene-THF + NADP <> 5,10-Methenyltetrahydrofolate + NADPH + Hydrogen ion
L-Serine + Tetrahydrofolic acid <> Glycine + Water + 5,10-Methylene-THF
dUMP + 5,10-Methylene-THF <> Dihydrofolic acid + 5-Thymidylic acid
2 Hydrogen ion + 5,10-Methylene-THF + NADH > 5-Methyltetrahydrofolic acid + NAD
5,10-Methylene-THF + Glycine + Water <> Tetrahydrofolic acid + L-Serine
5,10-Methylene-THF + NADP <> 5,10-Methenyltetrahydrofolate + NADPH
Glycine + Tetrahydrofolic acid + NAD <> 5,10-Methylene-THF + Ammonia + Carbon dioxide + NADH + Hydrogen ion
5-Methyltetrahydrofolic acid + NADP <> 5,10-Methylene-THF + NADPH + Hydrogen ion
5,10-Methylene-THF + alpha-Ketoisovaleric acid + Water <> Tetrahydrofolic acid + 2-Dehydropantoate
dUMP + 5,10-Methylene-THF <> Dihydrofolic acid + 5-Thymidylic acid
S-Aminomethyldihydrolipoylprotein + Tetrahydrofolic acid + S-Aminomethyldihydrolipoylprotein <> Dihydrolipoylprotein + 5,10-Methylene-THF + Ammonia
5-Methyltetrahydrofolic acid + NAD <> 5,10-Methylene-THF + NADH + Hydrogen ion
NAD + Glycine + Tetrahydrofolic acid > Hydrogen ion + 5,10-Methylene-THF + Ammonia + Carbon dioxide + NADH
Formaldehyde + Tetrahydrofolic acid > 5,10-Methylene-THF + Water
5-Methyltetrahydrofolic acid + NAD <> 5,10-Methylene-THF + Hydrogen ion + NADH
Water + alpha-Ketoisovaleric acid + 5,10-Methylene-THF <> 2-Dehydropantoate + Tetrahydrofolic acid
L-Serine + Tetrahydrofolic acid <> 5,10-Methylene-THF + Glycine + Water
NADP + 5,10-Methylene-THF <> NADPH + 5,10-Methenyltetrahydrofolate
dUMP + 5,10-Methylene-THF > 5-Thymidylic acid + Dihydrofolic acid
5,10-Methylene-THF + NADP > 5,10-Methenyltetrahydrofolate + NADPH
[Protein]-S(8)-aminomethyldihydrolipoyllysine + Tetrahydrofolic acid > [protein]-dihydrolipoyllysine + 5,10-Methylene-THF + Ammonia
5,10-Methylene-THF + Glycine + Water > Tetrahydrofolic acid + L-Serine
5-Methyltetrahydrofolic acid + NAD(P)(+) > 5,10-Methylene-THF + NAD(P)H

SMPDB Pathways:
GLYCINE BIOSYNTHESISPW000808 ThumbThumb?image type=greyscaleThumb?image type=simple
Nitrogen metabolismPW000755 ThumbThumb?image type=greyscaleThumb?image type=simple
One Carbon Pool by Folate IPW001735 ThumbThumb?image type=greyscaleThumb?image type=simple
One carbon pool by folatePW000773 ThumbThumb?image type=greyscaleThumb?image type=simple
Pantothenate and CoA biosynthesisPW000828 ThumbThumb?image type=greyscaleThumb?image type=simple
Pyrimidine metabolismPW000942 ThumbThumb?image type=greyscaleThumb?image type=simple
KEGG Pathways:
EcoCyc Pathways:
Concentrations
Not Available
Spectra
Spectra:
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0001900000-be062f23f73faa80d72bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-06ri-1325900000-6420a9d99896c4388b81View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9543000000-544604a154db7e208558View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-0002900000-a88382f350a14348376cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-0329500000-4f7c559817bf6df5a24dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-02w9-1493000000-143061365aaedaec549cView in MoNA
References
References:
  • Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114. Pubmed: 22080510
  • Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. Pubmed: 21097882
  • van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25. Pubmed: 17765195
  • Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948. Pubmed: 18331064
Synthesis Reference:Agrawal, Nitish; Mihai, Cornelia; Kohen, Amnon. Microscale synthesis of isotopically labeled R-[6-xH]N5,N10-methylene-5,6,7,8-tetrahydrofolate as a cofactor for thymidylate synthase. Analytical Biochemistry (2004), 328(1), 44-50.
Material Safety Data Sheet (MSDS)Not Available
External Links:
ResourceLink
CHEBI ID15636
HMDB IDHMDB01533
Pubchem Compound ID445117
Kegg IDC00143
ChemSpider ID388320
Wikipedia5,10-methylenetetrahydrofolate
BioCyc IDMETHYLENE-THF
EcoCyc IDMETHYLENE-THF
Ligand ExpoMHF

Enzymes

General function:
Involved in catalytic activity
Specific function:
Interconversion of serine and glycine
Gene Name:
glyA
Uniprot ID:
P0A825
Molecular weight:
45316
Reactions
5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine.
General function:
Involved in thymidylate synthase activity
Specific function:
Provides the sole de novo source of dTMP for DNA biosynthesis. This protein also binds to its mRNA thus repressing its own translation
Gene Name:
thyA
Uniprot ID:
P0A884
Molecular weight:
30480
Reactions
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP.
General function:
Involved in oxidoreductase activity
Specific function:
Lipoamide dehydrogenase is a component of the glycine cleavage system as well as of the alpha-ketoacid dehydrogenase complexes
Gene Name:
lpdA
Uniprot ID:
P0A9P0
Molecular weight:
50688
Reactions
Protein N(6)-(dihydrolipoyl)lysine + NAD(+) = protein N(6)-(lipoyl)lysine + NADH.
General function:
Involved in methylenetetrahydrofolate reductase (NADPH) activity
Specific function:
5-methyltetrahydrofolate + NAD(P)(+) = 5,10- methylenetetrahydrofolate + NAD(P)H
Gene Name:
metF
Uniprot ID:
P0AEZ1
Molecular weight:
33102
Reactions
5-methyltetrahydrofolate + NAD(P)(+) = 5,10-methylenetetrahydrofolate + NAD(P)H.
General function:
Involved in nucleotide binding
Specific function:
Catalyzes the oxidation of 5,10- methylenetetrahydrofolate to 5,10-methenyltetrahydrofolate and then the hydrolysis of 5,10-methenyltetrahydrofolate to 10- formyltetrahydrofolate. This enzyme is specific for NADP
Gene Name:
folD
Uniprot ID:
P24186
Molecular weight:
31044
Reactions
5,10-methylenetetrahydrofolate + NADP(+) = 5,10-methenyltetrahydrofolate + NADPH.
5,10-methenyltetrahydrofolate + H(2)O = 10-formyltetrahydrofolate.
General function:
Involved in aminomethyltransferase activity
Specific function:
The glycine cleavage system catalyzes the degradation of glycine
Gene Name:
gcvT
Uniprot ID:
P27248
Molecular weight:
40146
Reactions
[Protein]-S(8)-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH(3).
General function:
Involved in 3-methyl-2-oxobutanoate hydroxymethyltransferase activity
Specific function:
Catalyzes the reversible reaction in which hydroxymethyl group from 5,10-methylenetetrahydrofolate is tranferred onto alpha-ketoisovalerate to form ketopantoate
Gene Name:
panB
Uniprot ID:
P31057
Molecular weight:
28237
Reactions
5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate + H(2)O = tetrahydrofolate + 2-dehydropantoate.
General function:
Involved in glycine dehydrogenase (decarboxylating) activity
Specific function:
The glycine cleavage system catalyzes the degradation of glycine. The P protein binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor; CO(2) is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein
Gene Name:
gcvP
Uniprot ID:
P33195
Molecular weight:
104376
Reactions
Glycine + H-protein-lipoyllysine = H-protein-S-aminomethyldihydrolipoyllysine + CO(2).
General function:
Amino acid transport and metabolism
Specific function:
The glycine cleavage system catalyzes the degradation of glycine. The H protein shuttles the methylamine group of glycine from the P protein to the T protein
Gene Name:
gcvH
Uniprot ID:
P0A6T9
Molecular weight:
13811