Record Information
Version2.0
Creation Date2012-05-31 13:54:35 -0600
Update Date2015-06-03 15:54:12 -0600
Secondary Accession Numbers
  • ECMDB01562
Identification
Name:N5-Formyl-H4F
DescriptionN5-Formyl-H4F is the active metabolite of folic acid. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid.
Structure
Thumb
Synonyms:
  • (6R,S)-5-Formyltetrahydrofolate
  • (6R,S)-5-Formyltetrahydrofolic acid
  • 10-Formyl-7,8-dihydrofolate
  • 10-Formyl-7,8-dihydrofolic acid
  • 5-CHO-THF
  • 5-Formyl-5,6,7,8-tetrahydrofolate
  • 5-Formyl-5,6,7,8-tetrahydrofolic acid
  • 5-formyl-H4F
  • 5-Formyl-THF
  • 5-Formyl-THF leucovorin
  • 5-Formyltetrahydrofolate
  • 5-Formyltetrahydrofolic acid
  • 5-Formyltetrahydropteroylglutamate
  • 5-Formyltetrahydropteroylglutamic acid
  • Citrovorum factor
  • Folinate
  • Folinate-SF
  • Folinic acid
  • Folinic acid-SF
  • Formyl-H4F
  • L-Leucovorin
  • L-N-[p-[[(2-Amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl)methyl]amino]benzoyl]-Glutamate
  • L-N-[p-[[(2-Amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl)methyl]amino]benzoyl]-Glutamic acid
  • Leucal
  • Levoleucovorin
  • N5-Formyl-5,6,7,8-tetrahydrofolate
  • N5-Formyl-5,6,7,8-tetrahydrofolic acid
  • N5-formyl-thf
  • N5-Formyltetrahydrofolate
  • N5-Formyltetrahydrofolic acid
  • N5-formyl-H4F
  • N5-formyl-THF
  • Welcovorin
Chemical Formula:C20H23N7O7
Weight:Average: 473.4393
Monoisotopic: 473.165896125
InChI Key:VVIAGPKUTFNRDU-UHFFFAOYSA-N
InChI:InChI=1S/C20H23N7O7/c21-20-25-16-15(18(32)26-20)27(9-28)12(8-23-16)7-22-11-3-1-10(2-4-11)17(31)24-13(19(33)34)5-6-14(29)30/h1-4,9,12-13,22H,5-8H2,(H,24,31)(H,29,30)(H,33,34)(H4,21,23,25,26,32)
CAS number:58-05-9
IUPAC Name:2-[(4-{[(2-amino-5-formyl-4-oxo-3,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid
Traditional IUPAC Name:2-[(4-{[(2-amino-5-formyl-4-oxo-3,6,7,8-tetrahydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid
SMILES:NC1=NC2=C(N(C=O)C(CNC3=CC=C(C=C3)C(=O)NC(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
  • Tertiary carboxylic acid amide
  • Secondary carboxylic acid amide
  • Amino acid or derivatives
  • Amino acid
  • Carboxamide group
  • Secondary amine
  • Carboxylic acid
  • Carboxylic acid derivative
  • Azacycle
  • Organooxygen compound
  • Carbonyl group
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Amine
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Primary amine
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Physical Properties
State:Solid
Charge:-2
Melting point:Not Available
Experimental Properties:
PropertyValueSource
Predicted Properties
PropertyValueSource
Water Solubility0.18 g/LALOGPS
logP-1.6ALOGPS
logP-2.3ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)3.47ChemAxon
pKa (Strongest Basic)2.81ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area215.55 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity126.66 m³·mol⁻¹ChemAxon
Polarizability46.54 ųChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Biological Properties
Cellular Locations:Cytoplasm
Reactions:
SMPDB Pathways:
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
KEGG Pathways:
EcoCyc Pathways:Not Available
Concentrations
Not Available
Spectra
Spectra:
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-004i-2332900000-5c40a0014d3bb486cb20View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-0fk9-7225198000-aa48aa22224db36842c7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0031900000-31498c227b611f3360eaView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a6r-0393400000-f81606ae4f4b27aadbacView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-1591000000-825bc8196995ef0bc1e3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0000900000-203ae236b032df3233d7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0umj-1131900000-5174748fd5288f6523fdView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0007-9674000000-192da85bfca095ec870eView in MoNA
References
References:
  • Bentivoglio G, Melica F, Cristoforoni P: Folinic acid in the treatment of human male infertility. Fertil Steril. 1993 Oct;60(4):698-701. Pubmed: 8405528
  • Birmingham BK, Greene DS: Analysis of folinic acid in human serum using high-performance liquid chromatography with amperometric detection. J Pharm Sci. 1983 Nov;72(11):1306-9. Pubmed: 6606033
  • Bunni MA, Priest DG: Human red blood cell-mediated metabolism of leucovorin [(R,S)5-formyltetrahydrofolate] Arch Biochem Biophys. 1991 May 1;286(2):633-7. Pubmed: 1897982
  • Garbis SD, Melse-Boonstra A, West CE, van Breemen RB: Determination of folates in human plasma using hydrophilic interaction chromatography-tandem mass spectrometry. Anal Chem. 2001 Nov 15;73(22):5358-64. Pubmed: 11816560
  • Jansman FG, Coenen JL, De Graaf JC, Tobi H, Sleijfer DT, Brouwers JR: Relationship between pharmacokinetics of 5-FU in plasma and in saliva, and toxicity of 5-fluorouracil/folinic acid. Anticancer Res. 2002 Nov-Dec;22(6B):3449-55. Pubmed: 12552938
  • Jardine LF, Ingram LC, Bleyer WA: Intrathecal leucovorin after intrathecal methotrexate overdose. J Pediatr Hematol Oncol. 1996 Aug;18(3):302-4. Pubmed: 8689347
  • Joulia JM, Pinguet F, Ychou M, Duffour J, Astre C, Bressolle F: Plasma and salivary pharmacokinetics of 5-fluorouracil (5-FU) in patients with metastatic colorectal cancer receiving 5-FU bolus plus continuous infusion with high-dose folinic acid. Eur J Cancer. 1999 Feb;35(2):296-301. Pubmed: 10448274
  • Kajiyama Y, Tsurumaru M, Udagawa H, Tsutsumi K, Kinoshita Y, Akiyama H: Relief of jaundice by 5-fluorouracil and folinic acid in patients with recurrent gastric cancer. Surg Oncol. 1996 Aug;5(4):177-81. Pubmed: 9067566
  • 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
  • Karakayali FY, Bayar S, Hazinedaroglu S, Sahin F, Karayalcin K: Does folinic acid have a choleretic effect on humans? Turk J Gastroenterol. 2003 Jun;14(2):102-5. Pubmed: 14614635
  • 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
  • Micke O, Bruns F, Schafer U, Kurowski R, Horst E, Willich N: CA 19-9 in the therapy monitoring and follow-up of locally advanced cancer of the exocrine pancreas treated with radiochemotherapy. Anticancer Res. 2003 Mar-Apr;23(2A):835-40. Pubmed: 12820309
  • Micke O, Hesselmann S, Bruns F, Horst E, Devries A, Schuller P, Willich N, Schafer U: Results and follow-up of locally advanced cancer of the exocrine pancreas treated with radiochemotherapy. Anticancer Res. 2005 May-Jun;25(3A):1523-30. Pubmed: 16033054
  • Perry TL, Applegarth DA, Evans ME, Hansen S, Jellum E: Metabolic studies of a family with massive formiminoglutamic aciduria. Pediatr Res. 1975 Mar;9(3):117-22. Pubmed: 235753
  • Pfeiffer CM, Fazili Z, McCoy L, Zhang M, Gunter EW: Determination of folate vitamers in human serum by stable-isotope-dilution tandem mass spectrometry and comparison with radioassay and microbiologic assay. Clin Chem. 2004 Feb;50(2):423-32. Epub 2003 Dec 11. Pubmed: 14670827
  • Pineda M, Ormazabal A, Lopez-Gallardo E, Nascimento A, Solano A, Herrero MD, Vilaseca MA, Briones P, Ibanez L, Montoya J, Artuch R: Cerebral folate deficiency and leukoencephalopathy caused by a mitochondrial DNA deletion. Ann Neurol. 2006 Feb;59(2):394-8. Pubmed: 16365882
  • Polyzos A, Kouraklis G, Giannopoulos A, Bramis J, Delladetsima JK, Sfikakis PP: Irinotecan as salvage chemotherapy for advanced small bowel adenocarcinoma: a series of three patients. J Chemother. 2003 Oct;15(5):503-6. Pubmed: 14598944
  • Ramaekers VT, Hausler M, Opladen T, Heimann G, Blau N: Psychomotor retardation, spastic paraplegia, cerebellar ataxia and dyskinesia associated with low 5-methyltetrahydrofolate in cerebrospinal fluid: a novel neurometabolic condition responding to folinic acid substitution. Neuropediatrics. 2002 Dec;33(6):301-8. Pubmed: 12571785
  • Sengelov L, von der Maase H, Lundbeck F, Barlebo H, Colstrup H, Engelholm SA, Krarup T, Madsen EL, Meyhoff HH, Mommsen S, Nielsen OS, Pedersen D, Steven K, Sorensen B: Neoadjuvant chemotherapy with cisplatin and methotrexate in patients with muscle-invasive bladder tumours. Acta Oncol. 2002;41(5):447-56. Pubmed: 12442921
  • Straw JA, Szapary D, Wynn WT: Pharmacokinetics of the diastereoisomers of leucovorin after intravenous and oral administration to normal subjects. Cancer Res. 1984 Jul;44(7):3114-9. Pubmed: 6609768
  • Vimercati A, Greco P, D'Apolito A, Angelici MC, Possenti A, Carbonara S, Selvaggi L: [Risk assessment of vertical transmission of Toxoplasma infections] Acta Biomed Ateneo Parmense. 2000;71 Suppl 1:537-40. Pubmed: 11424802
  • Zhu WY, Alliegro MA, Melera PW: The rate of folate receptor alpha (FR alpha) synthesis in folate depleted CHL cells is regulated by a translational mechanism sensitive to media folate levels, while stable overexpression of its mRNA is mediated by gene amplification and an increase in transcript half-life. J Cell Biochem. 2001 Mar 26;81(2):205-19. Pubmed: 11241661
Synthesis Reference:Zakrzewski, Sigmund F.; Sansone, Annette M. Preparation of folinic acid (N5-formyltetrahydro folic acid). Methods Enzymol. (1971), 18(Pt. B), 731-3.
Material Safety Data Sheet (MSDS)Not Available
External Links:
ResourceLink
CHEBI ID209153
HMDB IDHMDB01562
Pubchem Compound ID143
Kegg IDC03479
ChemSpider ID140
Wikipediafolinate
BioCyc ID5-FORMYL-THF
EcoCyc ID5-FORMYL-THF

Enzymes

General function:
Involved in catalytic activity
Specific function:
Interconversion of serine and glycine
Gene Name:
glyA
Uniprot ID:
P0A825
Molecular weight:
45316
Reactions
5,10-methylenetetrahydrofolate + glycine + H(2)O = tetrahydrofolate + L-serine.
General function:
Involved in aminomethyltransferase activity
Specific function:
The glycine cleavage system catalyzes the degradation of glycine
Gene Name:
gcvT
Uniprot ID:
P27248
Molecular weight:
40146
Reactions
[Protein]-S(8)-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10-methylenetetrahydrofolate + NH(3).
General function:
Involved in ATP binding
Specific function:
Specific function unknown
Gene Name:
ygfA
Uniprot ID:
P0AC28
Molecular weight:
21105