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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2019-07-23 05:44:41 UTC
HMDB IDHMDB0001056
Secondary Accession Numbers
  • HMDB01056
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
Data?1563860681
Synonyms
ValueSource
7,8-DihydrofolateChEBI
7,8-Dihydrofolic acidChEBI
7,8-DihydropteroylglutamateChEBI
DihydrofolateChEBI
N-(7,8-Dihydropteroyl)-L-glutamic acidChEBI
7,8-Dihydropteroylglutamic acidGenerator
N-(7,8-Dihydropteroyl)-L-glutamateGenerator
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
Dihydrofolate, (D)-isomerHMDB
Chemical FormulaC19H21N7O6
Average Molecular Weight443.4133
Monoisotopic Molecular Weight443.155331439
IUPAC Name(2S)-2-[(4-{[(2-amino-4-oxo-1,4,7,8-tetrahydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid
Traditional Namedihydrofolic acid
CAS Registry Number4033-27-6
SMILES
NC1=NC(=O)C2=C(NCC(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)=N2)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 KeyOZRNSSUDZOLUSN-LBPRGKRZSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as glutamic acid and derivatives. Glutamic acid and derivatives are compounds containing glutamic acid or a derivative thereof resulting from reaction of glutamic acid at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentGlutamic acid and derivatives
Alternative Parents
Substituents
  • Glutamic acid or derivatives
  • Hippuric acid or derivatives
  • Hippuric acid
  • N-acyl-alpha-amino acid
  • N-acyl-alpha amino acid or derivatives
  • Pterin
  • Aminobenzamide
  • Aminobenzoic acid or derivatives
  • Pteridine
  • Benzamide
  • Benzoic acid or derivatives
  • Benzoyl
  • Phenylalkylamine
  • Aniline or substituted anilines
  • Hydroxypyrimidine
  • Secondary aliphatic/aromatic amine
  • Dicarboxylic acid or derivatives
  • Benzenoid
  • Pyrimidine
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Amino acid
  • Secondary carboxylic acid amide
  • Ketimine
  • Carboxamide group
  • Carboxylic acid
  • Propargyl-type 1,3-dipolar organic compound
  • Secondary amine
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Azacycle
  • Organic oxygen compound
  • Imine
  • Hydrocarbon derivative
  • Carbonyl group
  • Amine
  • Organic oxide
  • Organonitrogen compound
  • Organopnictogen compound
  • Organooxygen compound
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Source:

Biological location:

Role

Industrial application:

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 g/LALOGPS
logP-0.93ALOGPS
logP-1.8ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)3.37ChemAxon
pKa (Strongest Basic)2.09ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area207.6 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity120.99 m³·mol⁻¹ChemAxon
Polarizability44.31 ųChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0002-2469100000-dfb9d32424c0c60215dcJSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00dl-3320390000-c5791f4954b5cefa68e1JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0322900000-3bd8be8b6fc531102b49JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-0952200000-3a44b5c375b9b981244fJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-004i-1930000000-71775fd6210c3e719dc1JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0113900000-62b9c33c60c2e2fd46c6JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00xv-1349500000-3d3bae7b4497b96fc55dJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9441000000-c0339a106358ca6d7221JSpectraViewer | MoNA
Biological Properties
Cellular Locations
  • Extracellular
  • Mitochondria
  • Lysosome
Biospecimen Locations
  • Blood
Tissue Locations
  • Liver
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
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 IDDB02015
Phenol Explorer Compound IDNot Available
FoodDB IDFDB022395
KNApSAcK IDC00007248
Chemspider ID89228
KEGG Compound IDC00415
BioCyc IDNot Available
BiGG ID34911
Wikipedia LinkDihydrofolic acid
METLIN ID5970
PubChem Compound98792
PDB IDNot Available
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. [PubMed: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 + Phosphate + 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