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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-02-11 01:04:53 UTC
HMDB IDHMDB01533
Secondary Accession Numbers
  • 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
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 KeyInChIKey=QYNUQALWYRSVHF-PZORYLMUSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPteridines and derivatives
Sub ClassPterins and derivatives
Direct ParentTetrahydrofolic acids
Alternative Parents
Substituents
  • Tetrahydrofolic acid
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • Hippuric acid
  • Hippuric acid or derivatives
  • Phenylimidazolidine
  • Aminobenzoic acid or derivatives
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Imidazopyrazine
  • Benzoic acid or derivatives
  • Benzamide
  • Aminobenzamide
  • Dialkylarylamine
  • Benzoyl
  • Secondary aliphatic/aromatic amine
  • Pyrimidone
  • Amino fatty acid
  • Fatty acyl
  • Imidolactam
  • Benzenoid
  • Pyrimidine
  • Primary aromatic amine
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Vinylogous amide
  • Imidazolidine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Lactam
  • Carboxamide group
  • Azacycle
  • Secondary amine
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Cyanoamino acid metabolism
  • Component of Glycine, serine and threonine metabolism
  • Component of Methane metabolism
  • Component of Nitrogen metabolism
  • Component of Pyrimidine metabolism
  • DNA component
ApplicationNot Available
Cellular locations
  • Mitochondria
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 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity123.96 m3·mol-1ChemAxon
Polarizability46 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Mitochondria
Biofluid Locations
  • Blood
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
3-Phosphoglycerate dehydrogenase deficiencySMP00721Not Available
Ammonia RecyclingSMP00009map00910
Beta Ureidopropionase DeficiencySMP00172Not Available
Cystathionine Beta-Synthase DeficiencySMP00177Not Available
Dihydropyrimidinase DeficiencySMP00178Not Available
Dihydropyrimidine Dehydrogenase Deficiency (DHPD)SMP00179Not Available
Dimethylglycine Dehydrogenase DeficiencySMP00242Not Available
Dimethylglycine Dehydrogenase DeficiencySMP00484Not Available
Folate malabsorption, hereditarySMP00724Not Available
Folate MetabolismSMP00053map00670
Glycine and Serine MetabolismSMP00004map00260
Glycine N-methyltransferase DeficiencySMP00222Not Available
Homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism, cblG complementation typeSMP00570Not Available
Hyperglycinemia, non-ketoticSMP00485Not Available
HypermethioninemiaSMP00341Not Available
Methionine Adenosyltransferase DeficiencySMP00221Not Available
Methionine MetabolismSMP00033map00270
Methotrexate PathwaySMP00432Not Available
Methylenetetrahydrofolate Reductase Deficiency (MTHFRD)SMP00543Not Available
Methylenetetrahydrofolate Reductase Deficiency (MTHFRD)SMP00340Not Available
MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy)SMP00202Not Available
Non Ketotic HyperglycinemiaSMP00223Not Available
Pyrimidine MetabolismSMP00046map00240
S-Adenosylhomocysteine (SAH) Hydrolase DeficiencySMP00214Not Available
sarcosine oncometabolite pathway SMP02313Not Available
SarcosinemiaSMP00244Not Available
UMP Synthase Deiciency (Orotic Aciduria)SMP00219Not Available
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
NuGOwiki LinkHMDB01533
Metagene LinkHMDB01533
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