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Record Information
Version5.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2022-09-22 17:45:12 UTC
HMDB IDHMDB0001562
Secondary Accession Numbers
Metabolite Identification
Common NameFolinic acid
DescriptionFolinic acid, also known as (6S)-leucovorin or levoleucovorin, 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. In humans, folinic acid is involved in the metabolic disorder called the methylenetetrahydrofolate reductase deficiency (mthfrd) pathway. Folinic acid has been detected, but not quantified in, a few different foods, such as anatidaes (Anatidae), chickens (Gallus gallus), and domestic pigs (Sus scrofa domestica). This could make folinic acid a potential biomarker for the consumption of these foods. Folinic acid is a primary metabolite. Primary metabolites are metabolically or physiologically essential metabolites. They are directly involved in an organism’s growth, development or reproduction. Based on a literature review a significant number of articles have been published on Folinic acid.
Structure
Thumb
Synonyms
Chemical FormulaC20H23N7O7
Average Molecular Weight473.4393
Monoisotopic Molecular Weight473.165896125
IUPAC Name(2S)-2-{[4-({[(6S)-2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid
Traditional Name(2S)-2-{[4-({[(6S)-2-amino-5-formyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid
CAS Registry Number68538-85-2
SMILES
NC1=NC(=O)C2=C(NC[C@H](CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)N2C=O)N1
InChI Identifier
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)/t12-,13-/m0/s1
InChI KeyVVIAGPKUTFNRDU-STQMWFEESA-N
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 Descriptors
Ontology
Physiological effectNot Available
Disposition
ProcessNot Available
RoleNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct TypeData SourceCCS Value (Å2)Reference
[M-H]-MetCCS_train_neg196.25930932474
[M+H]+MetCCS_train_pos196.9230932474
Predicted Molecular Properties
Predicted Chromatographic Properties
Spectra
Biological Properties
Cellular Locations
  • Extracellular
Biospecimen Locations
  • Blood
  • Urine
Tissue Locations
  • Bladder
  • Fibroblasts
  • Pancreas
  • Testis
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.0025 +/- 0.0036 uMAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothAsthma details
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB11596
Phenol Explorer Compound IDNot Available
FooDB IDFDB112383
KNApSAcK IDC00050578
Chemspider ID131714
KEGG Compound IDC03479
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkFolinic acid
METLIN IDNot Available
PubChem Compound149436
PDB IDNot Available
ChEBI ID63606
Food Biomarker OntologyNot Available
VMH ID5FTHF
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceZakrzewski, 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
General References

Enzymes

General function:
Involved in catalytic activity
Specific function:
Folate-dependent enzyme, that displays both transferase and deaminase activity. Serves to channel one-carbon units from formiminoglutamate to the folate pool. Binds and promotes bundling of vimentin filaments originating from the Golgi (By similarity).
Gene Name:
FTCD
Uniprot ID:
O95954
Molecular weight:
58925.93
Reactions
Folinic acid + Glutamic acid → Tetrahydrofolic acid + N-Formyl-L-glutamic aciddetails
Folinic acid + Glutamic acid → Tetrahydrofolic acid + N-Formyl-L-glutamic aciddetails
General function:
Involved in aminomethyltransferase activity
Specific function:
The glycine cleavage system catalyzes the degradation of glycine.
Gene Name:
AMT
Uniprot ID:
P48728
Molecular weight:
43945.65
Reactions
Folinic acid → 5,10-Methenyltetrahydrofolic acid + Waterdetails
General function:
Involved in ATP binding
Specific function:
Contributes to tetrahydrofolate metabolism. Helps regulate carbon flow through the folate-dependent one-carbon metabolic network that supplies carbon for the biosynthesis of purines, thymidine and amino acids.
Gene Name:
MTHFS
Uniprot ID:
P49914
Molecular weight:
16813.995
Reactions
Adenosine triphosphate + Folinic acid → ADP + Phosphate + 5,10-Methenyltetrahydrofolic aciddetails
Adenosine triphosphate + Folinic acid + Hydrogen Ion → ADP + Phosphate + 5,10-Methenyltetrahydrofolic 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
References
  1. Aschele C, Debernardis D, Bandelloni R, Cascinu S, Catalano V, Giordani P, Barni S, Turci D, Drudi G, Lonardi S, Gallo L, Maley F, Monfardini S: Thymidylate synthase protein expression in colorectal cancer metastases predicts for clinical outcome to leucovorin-modulated bolus or infusional 5-fluorouracil but not methotrexate-modulated bolus 5-fluorouracil. Ann Oncol. 2002 Dec;13(12):1882-92. [PubMed:12453856 ]
  2. Zhu AX, Puchalski TA, Stanton VP Jr, Ryan DP, Clark JW, Nesbitt S, Charlat O, Kelly P, Kreconus E, Chabner BA, Supko JG: Dihydropyrimidine dehydrogenase and thymidylate synthase polymorphisms and their association with 5-fluorouracil/leucovorin chemotherapy in colorectal cancer. Clin Colorectal Cancer. 2004 Feb;3(4):225-34. [PubMed:15025795 ]
  3. Smorenburg CH, Peters GJ, van Groeningen CJ, Noordhuis P, Smid K, van Riel AM, Dercksen W, Pinedo HM, Giaccone G: Phase II study of tailored chemotherapy for advanced colorectal cancer with either 5-fluouracil and leucovorin or oxaliplatin and irinotecan based on the expression of thymidylate synthase and dihydropyrimidine dehydrogenase. Ann Oncol. 2006 Jan;17(1):35-42. Epub 2005 Oct 26. [PubMed:16251201 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter
Gene Name:
ABCC2
Uniprot ID:
Q92887
Molecular weight:
174205.6
References
  1. Horikawa M, Kato Y, Tyson CA, Sugiyama Y: The potential for an interaction between MRP2 (ABCC2) and various therapeutic agents: probenecid as a candidate inhibitor of the biliary excretion of irinotecan metabolites. Drug Metab Pharmacokinet. 2002;17(1):23-33. [PubMed:15618649 ]
  2. Chen ZS, Robey RW, Belinsky MG, Shchaveleva I, Ren XQ, Sugimoto Y, Ross DD, Bates SE, Kruh GD: Transport of methotrexate, methotrexate polyglutamates, and 17beta-estradiol 17-(beta-D-glucuronide) by ABCG2: effects of acquired mutations at R482 on methotrexate transport. Cancer Res. 2003 Jul 15;63(14):4048-54. [PubMed:12874005 ]
General function:
Involved in ATP binding
Specific function:
May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes
Gene Name:
ABCC3
Uniprot ID:
O15438
Molecular weight:
169341.1
References
  1. Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. [PubMed:11585759 ]
  2. Chen ZS, Robey RW, Belinsky MG, Shchaveleva I, Ren XQ, Sugimoto Y, Ross DD, Bates SE, Kruh GD: Transport of methotrexate, methotrexate polyglutamates, and 17beta-estradiol 17-(beta-D-glucuronide) by ABCG2: effects of acquired mutations at R482 on methotrexate transport. Cancer Res. 2003 Jul 15;63(14):4048-54. [PubMed:12874005 ]
General function:
Involved in ATP binding
Specific function:
May be an organic anion pump relevant to cellular detoxification
Gene Name:
ABCC4
Uniprot ID:
O15439
Molecular weight:
149525.3
References
  1. Chen ZS, Lee K, Walther S, Raftogianis RB, Kuwano M, Zeng H, Kruh GD: Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer Res. 2002 Jun 1;62(11):3144-50. [PubMed:12036927 ]