Dihydrofolic acid (ECMDB01056) (M2MDB000235)

IdentificationTaxonomyPhysical PropertiesBiological PropertiesSpectraConcentrationsLinksReferencesEnzymes (4)XML
Proteins (985)
Record Information
Version2.0
Creation Date2012-05-31 13:03:59 -0600
Update Date2015-10-15 16:13:50 -0600
Secondary Accession Numbers
  • ECMDB01056
Identification
Name:Dihydrofolic 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
MOLSDFPDBSMILESInChI
Synonyms:
  • 7,8-Dihydro-L-folate
  • 7,8-Dihydro-L-folic acid
  • 7,8-Dihydrofolate
  • 7,8-Dihydrofolate monoglutamate
  • 7,8-Dihydrofolic acid
  • 7,8-Dihydropteroyl monoglutamate
  • 7,8-Dihydropteroyl monoglutamic acid
  • 7,8-Dihydropteroylglutamate
  • 7,8-Dihydropteroylglutamic acid
  • DHF
  • DHFA
  • Dihydrofolate
  • Dihydrofolic acid
  • FH2
  • H2PteGlu
  • H2PteGlu1
  • H2PteGlu1
  • L-N-[p-[[(2-Amino-7,8-dihydro-4-hydroxy-6-pteridinyl)methyl]amino]benzoyl]-Glutamate
  • L-N-[p-[[(2-Amino-7,8-dihydro-4-hydroxy-6-pteridinyl)methyl]amino]benzoyl]-Glutamic acid
  • N-(4-(((2-Amino-1,4,7,8-tetrahydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-L-Glutamate
  • N-(4-(((2-Amino-1,4,7,8-tetrahydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-L-Glutamic acid
  • N-(4-{[(2-Amino-4-oxo-3,4,7,8-tetrahydropteridin-6-yl)methyl]amino}benzoyl)-L-glutamate
  • N-(4-{[(2-Amino-4-oxo-3,4,7,8-tetrahydropteridin-6-yl)methyl]amino}benzoyl)-L-glutamic acid
  • N-(7,8-Dihydropteroyl)-L-glutamate
  • N-(7,8-Dihydropteroyl)-L-glutamic acid
  • N-[4-[[(2-Amino-1,4,7,8-tetrahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-Glutamate
  • N-[4-[[(2-Amino-1,4,7,8-tetrahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-Glutamic acid
  • N-[4-[[(2-Amino-3,4,7,8-tetrahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-Glutamate
  • N-[4-[[(2-Amino-3,4,7,8-tetrahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-Glutamic acid
Chemical Formula:C19H21N7O6
Weight:Average: 443.4133
Monoisotopic: 443.155331439
InChI Key:OZRNSSUDZOLUSN-LBPRGKRZSA-N
InChI: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
CAS number:4033-27-6
IUPAC Name:(4S)-4-carboxy-4-[(4-{[(2-imino-4-oxido-1,2,7,8-tetrahydropteridin-6-yl)methyl]amino}phenyl)formamido]butanoate
Traditional IUPAC Name:(4S)-4-carboxy-4-[(4-{[(2-imino-4-oxido-7,8-dihydro-1H-pteridin-6-yl)methyl]amino}phenyl)formamido]butanoate
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
Chemical Taxonomy
Description 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
  • Glutamic acid or derivatives
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • Hippuric acid
  • Hippuric acid or derivatives
  • Alpha-amino acid or derivatives
  • Aminobenzamide
  • Aminobenzoic acid or derivatives
  • Benzamide
  • Benzoic acid or derivatives
  • Benzoyl
  • Aniline or substituted anilines
  • Phenylalkylamine
  • Aminopyrimidine
  • Secondary aliphatic/aromatic amine
  • Pyrimidone
  • Dicarboxylic acid or derivatives
  • Benzenoid
  • Pyrimidine
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Vinylogous amide
  • Amino acid or derivatives
  • Secondary carboxylic acid amide
  • Amino acid
  • Carboxamide group
  • Secondary amine
  • Azacycle
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Primary amine
  • Organic anion
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
  • a tetrahydrofolate-glutamate (THF )
Physical Properties
State:Solid
Charge:-2
Melting point:Not Available
Experimental Properties:
PropertyValueSource
Predicted Properties
PropertyValueSource
Water Solubility0.11 g/LALOGPS
logP0.1ALOGPS
logP-1ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)3.4ChemAxon
pKa (Strongest Basic)2.44ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area214.25 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity153.39 m³·mol⁻¹ChemAxon
Polarizability43.53 ųChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Biological Properties
Cellular Locations:Cytoplasm
Reactions:
Dihydrofolic acid + Hydrogen ion + NADPH <> NADP + Tetrahydrofolic acid
Adenosine triphosphate + 7,8-Dihydropteroic acid + L-Glutamate <> ADP + Dihydrofolic acid + Hydrogen ion + Phosphate
dUMP + 5,10-Methylene-THF <> Dihydrofolic acid + 5-Thymidylic acid
Tetrahydrofolic acid + NAD <> Dihydrofolic acid + NADH + Hydrogen ion
Tetrahydrofolic acid + NADP <> Dihydrofolic acid + NADPH + Hydrogen ion
Dihydrofolic acid + NAD <> Folic acid + NADH + Hydrogen ion
Dihydrofolic acid + NADP <> Folic acid + NADPH + Hydrogen ion
Adenosine triphosphate + 7,8-Dihydropteroic acid + L-Glutamate <> ADP + Phosphate + Dihydrofolic acid
NADP + Tetrahydrofolic acid < Hydrogen ion + NADPH + Dihydrofolic acid
L-Glutamate + 7,8-Dihydropteroic acid + Adenosine triphosphate > Hydrogen ion + Dihydrofolic acid + Phosphate + ADP
dUMP + 5,10-Methylene-THF > 5-Thymidylic acid + Dihydrofolic acid
Tetrahydrofolic acid + NADP > Dihydrofolic acid + NADPH
Adenosine triphosphate + 7,8-Dihydropteroic acid + L-Glutamate > ADP + Inorganic phosphate + Dihydrofolic acid
Dihydrofolic acid + NADP + Dihydrofolic acid > Folic acid + NADPH + Hydrogen ion + NADPH
Dihydrofolic acid + NADPH + Hydrogen ion + Dihydrofolic acid + NADPH > Tetrahydrofolic acid + NADP + Tetrahydrofolic acid
7,8-dihydrofolate monoglutamate + Hydrogen ion + NADPH + Dihydrofolic acid + NADPH > NADP + Tetrahydrofolic acid + Tetrahydrofolic acid
Dihydrofolic acid + 5-Thymidylic acid + Dihydrofolic acid > 5,10-Methylene-THF + dUMP + 5,10-Methylene-THF
dUMP + 5,10-methenyltetrahydrofolate mono-L-glutamate + 5,10-methenyltetrahydrofolate mono-L-glutamate > Dihydrofolic acid + 5-Thymidylic acid + Dihydrofolic acid
7,8-Dihydropteroic acid + Adenosine triphosphate + L-Glutamic acid + L-Glutamate > Adenosine diphosphate + Phosphate + Hydrogen ion + 7,8-dihydrofolate monoglutamate + ADP + Dihydrofolic acid
dUMP + 5 5,10-Methylene-THF <> Dihydrofolic acid +5 5-Thymidylic acid
Dihydrofolic acid + Hydrogen ion + NADPH <> NADP + Tetrahydrofolic acid
Adenosine triphosphate + 7 7,8-Dihydropteroic acid + L-Glutamate <> ADP + Dihydrofolic acid + Hydrogen ion + Phosphate
dUMP + 5 5,10-Methylene-THF <> Dihydrofolic acid +5 5-Thymidylic acid
Dihydrofolic acid + Hydrogen ion + NADPH <> NADP + Tetrahydrofolic acid
Dihydrofolic acid + Hydrogen ion + NADPH <> NADP + Tetrahydrofolic acid
SMPDB Pathways:
Folate biosynthesisPW000908 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
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, Positivesplash10-0006-0000900000-a4c241fffe12ab7ef28aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00ke-0000900000-e2649a4064245971e04dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0f92-0322900000-85ce91e6ef3aba9bebc6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0000900000-4a414bcefb3680421e86View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-2000900000-d371fff550aea75cc643View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9100000000-f0cf9e2f8e9df68bdc25View 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
  • 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
  • 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:Smith, 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)
External Links:
ResourceLink
CHEBI ID15633
HMDB IDHMDB01056
Pubchem Compound ID98792
Kegg IDC00415
ChemSpider ID89228
WikipediaDihydrofolate
BioCyc IDDIHYDROFOLATE
EcoCyc IDDIHYDROFOLATE
Ligand ExpoDHF

Enzymes

Protein Details
1. Bifunctional protein folC
General function:
Involved in tetrahydrofolylpolyglutamate synthase activity
Specific function:
Conversion of folates to polyglutamate derivatives
Gene Name:
folC
Uniprot ID:
P08192
Molecular weight:
45405
Reactions
ATP + tetrahydropteroyl-(gamma-Glu)(n) + L-glutamate = ADP + phosphate + tetrahydropteroyl-(gamma-Glu)(n+1).
ATP + 7,8-dihydropteroate + L-glutamate = ADP + phosphate + 7,8-dihydropteroylglutamate.
Protein Details
2. Thymidylate synthase
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.
Protein Details
3. Dihydrofolate reductase
General function:
Involved in dihydrofolate reductase activity
Specific function:
Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis
Gene Name:
folA
Uniprot ID:
P0ABQ4
Molecular weight:
17999
Reactions
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH.
Protein Details
4. Dihydrofolate reductase folM
General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes the reduction of dihydrofolate to tetrahydrofolate
Gene Name:
folM
Uniprot ID:
P0AFS3
Molecular weight:
26348
Reactions
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH.