ECMDB: N5-Formyl-H4F (ECMDB01562) (M2MDB000421)

Identification Taxonomy Physical Properties Biological Properties Spectra Concentrations Links References Enzymes (3)XML

Proteins (706)

Record Information

Version

2.0

Creation Date

2012-05-31 13:54:35 -0600

Update Date

2015-06-03 15:54:12 -0600

Secondary Accession Numbers

ECMDB01562

Identification

Name:

N5-Formyl-H4F

Description

N5-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

MOL SDF PDB SMILES InChI

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.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Pteridines and derivatives

Sub Class

Pterins and derivatives

Direct Parent

Tetrahydrofolic 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 Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Physical Properties

State:

Solid

Charge:

-2

Melting point:

Not Available

Experimental Properties:

Property	Value	Source

Predicted Properties

Property	Value	Source
Water Solubility	0.18 g/L	ALOGPS
logP	-1.6	ALOGPS
logP	-2.3	ChemAxon
logS	-3.4	ALOGPS
pKa (Strongest Acidic)	3.47	ChemAxon
pKa (Strongest Basic)	2.81	ChemAxon
Physiological Charge	-2	ChemAxon
Hydrogen Acceptor Count	11	ChemAxon
Hydrogen Donor Count	7	ChemAxon
Polar Surface Area	215.55 Å²	ChemAxon
Rotatable Bond Count	9	ChemAxon
Refractivity	126.66 m³·mol⁻¹	ChemAxon
Polarizability	46.54 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Biological Properties

Cellular Locations:

Cytoplasm

Reactions:

SMPDB Pathways:

One Carbon Pool by Folate I	PW001735
One carbon pool by folate	PW000773

KEGG Pathways:

Metabolic pathways eco01100
One carbon pool by folate ec00670

EcoCyc Pathways:

Not Available

Concentrations

Not Available

Spectra

Spectra:

Spectrum Type	Description	Splash Key
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-004i-2332900000-5c40a0014d3bb486cb20	View in MoNA
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positive	splash10-0fk9-7225198000-aa48aa22224db36842c7	View in MoNA
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_5) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_6) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_7) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_7) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_8) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_9) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_10) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_11) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_12) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_13) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_14) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_15) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_16) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_17) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_19) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_20) - 70eV, Positive	Not Available	View in JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0a4i-0031900000-31498c227b611f3360ea	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0a6r-0393400000-f81606ae4f4b27aadbac	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4i-1591000000-825bc8196995ef0bc1e3	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-00di-0000900000-203ae236b032df3233d7	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0umj-1131900000-5174748fd5288f6523fd	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0007-9674000000-192da85bfca095ec870e	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-00b9-0018900000-5cbc8e2351f8b3ec2868	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-004i-0139300000-a45a2d1a5cd350ef7860	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0012-1956000000-611d4066a036a7ff475f	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-00di-0001900000-20cea700a6b8ce876f5e	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0fb9-1304900000-85021f1e80280eb64d56	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0fba-3517900000-75ddfa6e2a4565261466	View in MoNA
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	View in JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	View in JSpectraViewer

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

Links

External Links:

Resource	Link
CHEBI ID	Not Available
HMDB ID	HMDB01562
Pubchem Compound ID	143
Kegg ID	C03479
ChemSpider ID	140
Wikipedia	folinate
BioCyc ID	5-FORMYL-THF
EcoCyc ID	5-FORMYL-THF

Enzymes

Protein Details

1. Serine hydroxymethyltransferase

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.

Protein Details

2. Aminomethyltransferase

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).

Protein Details

3. Uncharacterized protein ygfA

General function:: Involved in ATP binding
Specific function:: Specific function unknown
Gene Name:: ygfA
Uniprot ID:: P0AC28
Molecular weight:: 21105

N5-Formyl-H4F (ECMDB01562) (M2MDB000421)

Structure for #<Compound:0x9dac2978>

Enzymes

Reactions

Reactions