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Record Information
Version4.0
Creation Date2005-11-16 15:48:42 UTC
Update Date2017-09-27 08:24:08 UTC
HMDB IDHMDB0001533
Secondary Accession Numbers
  • HMDB01533
  • HMDB02365
Metabolite Identification
Common Name5,10-Methylene-THF
Description5,10-Methylene-THF is an intermediate in glycine, serine and threonine metabolism and one carbon metabolism. 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. 5,10-Methylene-THF is a substrate for Methylenetetrahydrofolate reductase. This enzyme converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. This reaction is required for the multistep process that converts the amino acid homocysteine to methionine. The body uses methionine to make proteins and other important compounds. 5,10-CH2-THF is a substrate for many enzymes including Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase (mitochondrial), Aminomethyltransferase (mitochondrial), Serine hydroxymethyltransferase (mitochondrial), Methylenetetrahydrofolate reductase, C-1-tetrahydrofolate synthase (cytoplasmic), Serine hydroxymethyltransferase (cytosolic) and Thymidylate synthase.
Structure
Thumb
Synonyms
ValueSource
(6R)-5,10-MethylenetetrahydrofolateKegg
(6R)-5,10-Methylenetetrahydrofolic acidGenerator
5,10-MethenyltetrahydropteroylglutamateHMDB
5,10-Methylene-6-hydrofolateHMDB
5,10-Methylene-6-hydrofolic acidHMDB
5,10-MethylenetetrahydrofolateHMDB
5,10-Methylenetetrahydrofolic acidHMDB
N5>,N10-methylenetetrahydrofolateHMDB
5,10-Methylene-5,6,7,8-tetrahydrofolateMeSH
TetrahydromethylenefolateMeSH
5,10-Methylenetetrahydrofolate, (D-glu)-isomerMeSH
CH2H4FolateMeSH
5,10-Methylenetetrahydrofolate monohydrochloride, (L-glu)-isomerMeSH
5,10-Methylenetetrahydrofolate, (L-glu)-(S)-isomerMeSH
Chemical FormulaC20H23N7O6
Average Molecular Weight457.4399
Monoisotopic Molecular Weight457.170981503
IUPAC Name2-({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 Name2-({4-[(6aR)-3-amino-1-oxo-2H,5H,6H,6aH,7H,9H-imidazolidino[1,5-f]pteridin-8-yl]phenyl}formamido)pentanedioic acid
CAS Registry Number31690-11-6
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
InChI Identifier
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
InChI KeyQYNUQALWYRSVHF-PZORYLMUSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as tetrahydrofolic acids. These are heterocyclic compounds based on the 5,6,7,8-tetrahydropteroic acid skeleton conjugated with at least one L-glutamic acid unit.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassPteridines and derivatives
Direct ParentTetrahydrofolic acids
Alternative Parents
Substituents
  • Tetrahydrofolic acid
  • Glutamic acid or derivatives
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • Hippuric acid or derivatives
  • Hippuric acid
  • Phenylimidazolidine
  • Alpha-amino acid or derivatives
  • Benzamide
  • Benzoic acid or derivatives
  • Imidazopyrazine
  • Benzoyl
  • Aniline or substituted anilines
  • Dialkylarylamine
  • Aminopyrimidine
  • Secondary aliphatic/aromatic amine
  • Pyrimidone
  • Dicarboxylic acid or derivatives
  • Pyrimidine
  • Monocyclic benzene moiety
  • Benzenoid
  • Primary aromatic amine
  • Heteroaromatic compound
  • Vinylogous amide
  • Imidazolidine
  • Secondary carboxylic acid amide
  • Amino acid or derivatives
  • Amino acid
  • Carboxamide group
  • Azacycle
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organooxygen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Amine
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Primary amine
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

Disposition

Biological Location:

  Biofluid and excreta:

Source:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
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
Polarizability46 ųChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-03di-1635900000-4b2ed6618451a7e931b1View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-001i-2129050000-80e96fb3203322200945View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-08fu-0003900000-ce1f75a98c0216d169e2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-0229400000-c8c29bf14ef80a73f864View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-02u3-1192000000-ab556f50884c7b4fdcbeView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0001900000-6ba3ddeb1f652fdc6b6bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-08fr-1225900000-82b75909f87dfeb54211View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9553000000-5aca24c246430955de51View in MoNA
Biological Properties
Cellular Locations
  • Mitochondria
Biofluid Locations
  • Blood
Tissue LocationNot Available
Pathways
NameSMPDB/PathwhizKEGG
3-Phosphoglycerate dehydrogenase deficiencyPw000698Pw000698 greyscalePw000698 simpleNot Available
Ammonia RecyclingPw000009Pw000009 greyscalePw000009 simpleMap00910
Beta Ureidopropionase DeficiencyPw000187Pw000187 greyscalePw000187 simpleNot Available
Cystathionine Beta-Synthase DeficiencyPw000100Pw000100 greyscalePw000100 simpleNot Available
Dihydropyrimidinase DeficiencyPw000189Pw000189 greyscalePw000189 simpleNot Available
Displaying entries 1 - 5 of 26 in total
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.01 (0.0-0.21) uMAdult (>18 years old)BothNormal details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022675
KNApSAcK IDNot Available
Chemspider ID388320
KEGG Compound IDC00143
BioCyc IDMETHYLENE-THF
BiGG ID34022
Wikipedia Link5,10-methylenetetrahydrofolate
METLIN ID6304
PubChem Compound439175
PDB IDNot Available
ChEBI ID15636
References
Synthesis ReferenceAgrawal, 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
General ReferencesNot Available

Enzymes

General function:
Involved in methylenetetrahydrofolate reductase (NADPH) activity
Specific function:
Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine.
Gene Name:
MTHFR
Uniprot ID:
P42898
Molecular weight:
74595.895
Reactions
5-Methyltetrahydrofolic acid + NAD(P)(+) → 5,10-Methylene-THF + NAD(P)Hdetails
5-Methyltetrahydrofolic acid + NADP → 5,10-Methylene-THF + NADPH + Hydrogen Iondetails
5-Methyltetrahydrofolic acid + NAD → 5,10-Methylene-THF + NADH + Hydrogen Iondetails
General function:
Involved in aminomethyltransferase activity
Specific function:
The glycine cleavage system catalyzes the degradation of glycine.
Gene Name:
AMT
Uniprot ID:
P48728
Molecular weight:
43945.65
Reactions
[Protein]-S(8)-aminomethyldihydrolipoyllysine + Tetrahydrofolic acid → [protein]-dihydrolipoyllysine + 5,10-Methylene-THF + Ammoniadetails
Glycine + Tetrahydrofolic acid + NAD → 5,10-Methylene-THF + Ammonia + Carbon dioxide + NADH + Hydrogen Iondetails
S-Aminomethyldihydrolipoylprotein + Tetrahydrofolic acid → Dihydrolipoylprotein + 5,10-Methylene-THF + Ammoniadetails
General function:
Involved in catalytic activity
Specific function:
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Required to prevent uracil accumulation in mtDNA. Interconversion of serine and glycine. Associates with mitochondrial DNA.
Gene Name:
SHMT2
Uniprot ID:
P34897
Molecular weight:
54862.125
Reactions
5,10-Methylene-THF + Glycine + Water → Tetrahydrofolic acid + L-Serinedetails
General function:
Involved in catalytic activity
Specific function:
Interconversion of serine and glycine.
Gene Name:
SHMT1
Uniprot ID:
P34896
Molecular weight:
53082.18
Reactions
5,10-Methylene-THF + Glycine + Water → Tetrahydrofolic acid + L-Serinedetails
General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
MTHFD2
Uniprot ID:
P13995
Molecular weight:
37894.775
Reactions
5,10-Methylene-THF + NAD → 5,10-Methenyltetrahydrofolic acid + NADHdetails
General function:
Involved in formate-tetrahydrofolate ligase activity
Specific function:
Not Available
Gene Name:
MTHFD1
Uniprot ID:
P11586
Molecular weight:
101530.36
Reactions
5,10-Methylene-THF + NADP → 5,10-Methenyltetrahydrofolic acid + NADPHdetails
General function:
Involved in glycine catabolic process
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:
GCSH
Uniprot ID:
P23434
Molecular weight:
Not Available
Reactions
Glycine + Tetrahydrofolic acid + NAD → 5,10-Methylene-THF + Ammonia + Carbon dioxide + NADH + Hydrogen Iondetails
General function:
Involved in thymidylate synthase activity
Specific function:
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
Gene Name:
TYMS
Uniprot ID:
P04818
Molecular weight:
35715.65
Reactions
5,10-Methylene-THF + dUMP → Dihydrofolic acid + 5-Thymidylic aciddetails
General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
MTHFD2L
Uniprot ID:
Q9H903
Molecular weight:
37315.11
Reactions
5,10-Methylene-THF + NAD → 5,10-Methenyltetrahydrofolic acid + NADHdetails
General function:
Involved in formate-tetrahydrofolate ligase activity
Specific function:
May provide the missing metabolic reaction required to link the mitochondria and the cytoplasm in the mammalian model of one-carbon folate metabolism in embryonic an transformed cells complementing thus the enzymatic activities of MTHFD2 (By similarity).
Gene Name:
MTHFD1L
Uniprot ID:
Q6UB35
Molecular weight:
105888.19
General function:
Involved in catalytic activity
Specific function:
Not Available
Gene Name:
MTHFD2
Uniprot ID:
Q7Z650
Molecular weight:
26849.1