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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-02-11 01:03:46 UTC
HMDB IDHMDB01056
Secondary Accession NumbersNone
Metabolite Identification
Common NameDihydrofolic acid
DescriptionDihydrofolic acid is a folic acid derivative acted upon by dihydrofolate reductase to produce tetrahydrofolic acid. It interacts with bacteria during cell division. It can be targeted with drug analogs to prevent nucleic acid synthesis. Dihydrofolic acid is also known by the name Dihydrofolate - more commonly Vitamin B9.
Structure
Thumb
Synonyms
ValueSource
7,8-DihydrofolateChEBI
7,8-Dihydrofolic acidChEBI
7,8-DihydropteroylglutamateChEBI
DihydrofolateChEBI
N-(7,8-Dihydropteroyl)-L-glutamic acidChEBI
7,8-dihydro-L-Folic acidHMDB
H2PteGluHMDB
H2PteGlu1HMDB
L-N-[P-[[(2-amino-7,8-dihydro-4-Hydroxy-6-pteridinyl)methyl]amino]benzoyl]-glutamic acidHMDB
N-(4-(((2-amino-1,4,7,8-tetrahydro-4-oxo-6-Pteridinyl)methyl)amino)benzoyl)-L-glutamic acidHMDB
N-(4-{[(2-amino-4-oxo-3,4,7,8-tetrahydropteridin-6-yl)methyl]amino}benzoyl)-L-glutamic acidHMDB
N-[4-[[(2-amino-1,4,7,8-tetrahydro-4-oxo-6-Pteridinyl)methyl]amino]benzoyl]-L-glutamic acidHMDB
N-[4-[[(2-amino-3,4,7,8-tetrahydro-4-oxo-6-Pteridinyl)methyl]amino]benzoyl]-L-glutamic acidHMDB
Vitamin b9HMDB
Chemical FormulaC19H21N7O6
Average Molecular Weight443.4133
Monoisotopic Molecular Weight443.155331439
IUPAC Name(2S)-2-[(4-{[(2-amino-4-oxo-3,4,7,8-tetrahydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid
Traditional Namedihydrofolic acid
CAS Registry Number4033-27-6
SMILES
NC1=NC2=C(N=C(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)CN2)C(=O)N1
InChI Identifier
InChI=1S/C19H21N7O6/c20-19-25-15-14(17(30)26-19)23-11(8-22-15)7-21-10-3-1-9(2-4-10)16(29)24-12(18(31)32)5-6-13(27)28/h1-4,12,21H,5-8H2,(H,24,29)(H,27,28)(H,31,32)(H4,20,22,25,26,30)/t12-/m0/s1
InChI KeyInChIKey=OZRNSSUDZOLUSN-LBPRGKRZSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as dihydrofolic acids and derivatives. These are heterocyclic compounds based on the 5,6-dihydropteroic acid/7,8-dihydropteroic acid skeleton conjugated with one or more L-glutamic acid units (or derivative thereof).
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPteridines and derivatives
Sub ClassPterins and derivatives
Direct ParentDihydrofolic acids and derivatives
Alternative Parents
Substituents
  • Dihydrofolic acid or derivatives
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • Hippuric acid
  • Hippuric acid or derivatives
  • Aminobenzoic acid or derivatives
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Benzoic acid or derivatives
  • Benzamide
  • Aminobenzamide
  • Phenylalkylamine
  • Substituted aniline
  • Benzoyl
  • Secondary aliphatic/aromatic amine
  • Pyrimidone
  • Aniline
  • Amino fatty acid
  • Fatty acyl
  • Imidolactam
  • Benzenoid
  • Pyrimidine
  • Primary aromatic amine
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Vinylogous amide
  • Secondary carboxylic acid amide
  • Lactam
  • Ketimine
  • Carboxamide group
  • Azacycle
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Secondary amine
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Imine
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Folate biosynthesis
  • Component of Pyrimidine metabolism
ApplicationNot Available
Cellular locations
  • Extracellular
  • Mitochondria
  • Lysosome
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 Solubility0.12 mg/mLALOGPS
logP-1.6ALOGPS
logP-2.1ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)3.16ChemAxon
pKa (Strongest Basic)3.68ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area207.6 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity121.19 m3·mol-1ChemAxon
Polarizability44.38 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0322900000-3bd8be8b6fc531102b49View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-0952200000-3a44b5c375b9b981244fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-004i-1930000000-71775fd6210c3e719dc1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0113900000-62b9c33c60c2e2fd46c6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00xv-1349500000-3d3bae7b4497b96fc55dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9441000000-c0339a106358ca6d7221View in MoNA
Biological Properties
Cellular Locations
  • Extracellular
  • Mitochondria
  • Lysosome
Biofluid Locations
  • Blood
Tissue Location
  • Liver
Pathways
NameSMPDB LinkKEGG Link
Beta Ureidopropionase DeficiencySMP00172Not Available
Dihydropyrimidinase DeficiencySMP00178Not Available
Folate malabsorption, hereditarySMP00724Not Available
Folate MetabolismSMP00053map00670
Methotrexate PathwaySMP00432Not Available
Methylenetetrahydrofolate Reductase Deficiency (MTHFRD)SMP00543Not Available
MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy)SMP00202Not Available
Pterine BiosynthesisSMP00005map00790
Pyrimidine MetabolismSMP00046map00240
UMP Synthase Deiciency (Orotic Aciduria)SMP00219Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.005 +/- 0.001 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 IDFDB022395
KNApSAcK IDNot Available
Chemspider ID89228
KEGG Compound IDC00415
BioCyc IDDIHYDROFOLATE
BiGG ID34911
Wikipedia LinkDihydrofolate
NuGOwiki LinkHMDB01056
Metagene LinkHMDB01056
METLIN ID5970
PubChem Compound98792
PDB IDDHF
ChEBI ID15633
References
Synthesis ReferenceSmith, Karin; Scrimgeour, K. G.; Huennekens, F. M. Folic acid coenzymes and one-carbon metabolism. XV. Synthesis of a new form of dihydrofolate. Biochemical and Biophysical Research Communications (1963), 11(5), 388-92.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Navarro-Peran E, Cabezas-Herrera J, Garcia-Canovas F, Durrant MC, Thorneley RN, Rodriguez-Lopez JN: The antifolate activity of tea catechins. Cancer Res. 2005 Mar 15;65(6):2059-64. [15781612 ]

Enzymes

General function:
Involved in dihydrofolate reductase activity
Specific function:
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.
Gene Name:
DHFR
Uniprot ID:
P00374
Molecular weight:
21452.61
Reactions
Tetrahydrofolic acid + NADP → Dihydrofolic acid + NADPHdetails
Tetrahydrofolic acid + NAD → Dihydrofolic acid + NADH + Hydrogen Iondetails
Tetrahydrofolic acid + NADP → Dihydrofolic acid + NADPH + Hydrogen Iondetails
Dihydrofolic acid + NAD → Folic acid + NADH + Hydrogen Iondetails
Dihydrofolic acid + NADP → Folic acid + NADPH + Hydrogen Iondetails
General function:
Involved in tetrahydrofolylpolyglutamate synthase activity
Specific function:
Catalyzes conversion of folates to polyglutamate derivatives allowing concentration of folate compounds in the cell and the intracellular retention of these cofactors, which are important substrates for most of the folate-dependent enzymes that are involved in one-carbon transfer reactions involved in purine, pyrimidine and amino acid synthesis. Unsubstitued reduced folates are the preferred substrates. Metabolizes methotrexate (MTX) to polyglutamates.
Gene Name:
FPGS
Uniprot ID:
Q05932
Molecular weight:
59173.37
Reactions
Adenosine triphosphate + 7,8-Dihydropteroic acid + L-Glutamic acid → ADP + Phosphoric acid + Dihydrofolic aciddetails
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 dihydrofolate reductase activity
Specific function:
Not Available
Gene Name:
DYR
Uniprot ID:
B0YJ76
Molecular weight:
21452.6
General function:
Not Available
Specific function:
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Required to prevent uracil accumulation in mtDNA. Binds its own mRNA and that of DHFR.
Gene Name:
DHFRL1
Uniprot ID:
Q86XF0
Molecular weight:
21619.88
Reactions
Tetrahydrofolic acid + NADP → Dihydrofolic acid + NADPHdetails
Tetrahydrofolic acid + NAD → Dihydrofolic acid + NADH + Hydrogen Iondetails
Tetrahydrofolic acid + NADP → Dihydrofolic acid + NADPH + Hydrogen Iondetails
Dihydrofolic acid + NAD → Folic acid + NADH + Hydrogen Iondetails
Dihydrofolic acid + NADP → Folic acid + NADPH + Hydrogen Iondetails