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Identification
Name Folic Acid
Accession Number DB00158 (NUTR00025)
Type small molecule
Groups approved, nutraceutical
Description

A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (poaceae). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Folate
Pteroyl-L-glutamic acid
Pteroyl-L-monoglutamic acid
Pteroylglutamic acid
Pteroylmonoglutamic acid
Vitamin B9
Vitamin Bc
Vitamin Be
Vitamin M
Salts Not Available
Brand names
Name Company
Acifolic
Apo-Folic
Cytofol
Dosfolat B activ
Folacid
Folacin
Folbal
Folcidin
Foldine
Folettes
Foliamin
Folicet
Folipac
Folsan
Folsaure
Folsav
Folvite
Folvron
Incafolic
Millafol
First Prev Next Last
Brand mixtures Not Available
Categories
  • Dietary supplement
  • Micronutrient
  • Vitamin B Complex
  • Hematinics
CAS number 59-30-3
Weight Average: 441.3975
Monoisotopic: 441.139681375
Chemical Formula C19H19N7O6
InChI Key InChIKey=OVBPIULPVIDEAO-LBPRGKRZSA-N
InChI
InChI=1S/C19H19N7O6/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/h1-4,8,12,21H,5-7H2,(H,24,29)(H,27,28)(H,31,32)(H3,20,22,25,26,30)/t12-/m0/s1
Plain Text
IUPAC Name
(2S)-2-[(4-{[(2-amino-4-oxo-1,4-dihydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid
SMILES
NC1=NC(=O)C2=NC(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)=CN=C2N1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Pterins
  • Keto-Acids
  • Amino Acids
Substructures
  • Pterins
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Amino Ketones
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Pyrimidines and Derivatives
  • Pyrazines
  • Heterocyclic compounds
  • Aromatic compounds
  • Keto-Acids
  • Carboxamides and Derivatives
  • Pteridines
  • Amino Acids
  • Imines
  • Benzoyl Derivatives
  • Cyanamides
  • Benzamides
  • Anilines
Pharmacology
Indication For treatment of folic acid deficiency, megaloblastic anemia and in anemias of nutritional supplements, pregnancy, infancy, or childhood.
Pharmacodynamics Folic acid, a water-soluble B-complex vitamin, is found in foods such as liver, kidneys, yeast, and leafy, green vegetables. Folic acid is used to diagnose folate deficiency and to treat topical sprue and megaloblastic and macrocytic anemias, hematologic complications resulting from a deficiency in folic acid.
Mechanism of action Folic acid, as it is biochemically inactive, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase. These folic acid congeners are transported across cells by receptor-mediated endocytosis where they are needed to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate. Using vitamin B12 as a cofactor, folic acid can normalize high homocysteine levels by remethylation of homocysteine to methionine via methionine synthetase.
Absorption Not Available
Volume of distribution Not Available
Protein binding Very high to plasma protein
Metabolism Hepatic
Route of elimination Folic Acid is metabolized in the liver to 7, 8-dihydrofolic acid and eventually to 5,6,7,8-tetrahydrofolic acid with the aid of reduced diphosphopyridine nucleotide (DPNH) and folate reductases. A majority of the metabolic products appeared in the urine after 6 hours; excretion was generally complete within 24 hours. Folic Acid is also excreted in the milk of lactating mothers.
Half life Not Available
Clearance Not Available
Toxicity IPR-MUS LD50 85 mg/kg,IVN-GPG LD50 120 mg/kg, IVN-MUS LD50 239 mg/kg, IVN-RAT LD50 500 mg/kg, IVN-RBT LD50 410 mg/kg
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • App pharmaceuticals llc
  • Ben venue laboratories inc
  • Wyeth pharmaceuticals inc
  • Barr laboratories inc
  • Cadista pharmaceuticals inc
  • Contract pharmacal corp
  • Everylife
  • Excellium pharmaceutical inc
  • Halsey drug co inc
  • Impax laboratories inc
  • Invagen pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Lannett co inc
  • Eli lilly and co
  • Mk laboratories inc
  • Mutual pharmaceutical co inc
  • Nexgen pharma inc
  • Pharmax group inc
  • Pharmeral inc
  • Pioneer pharmaceuticals inc
  • Purepac pharmaceutical co
  • Sandoz inc
  • Tablicaps inc
  • Udl laboratories inc
  • Usl pharma inc
  • Valeant pharmaceuticals international
  • Vangard laboratories inc div midway medical co
  • Vintage pharmaceuticals llc
  • Vintage pharmaceuticals inc
  • Watson laboratories
  • Watson laboratories inc
  • West ward pharmaceutical corp
  • Whiteworth towne paulsen inc
  • Mission pharmacal co
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Liquid Intravenous
Tablet Oral
Prices
Unit description Cost Unit
Folic acid 5 mg/ml vial 2.14 USD ml
Folic Acid 5 mg/ml 2.04 USD ml
Folic acid powder 1.68 USD g
Folvite 5 mg/ml vial 1.38 USD ml
Folic Acid 1 mg tablet 0.15 USD tablet
Folic acid 400 mcg tablet 0.07 USD tablet
Apo-Folic 5 mg Tablet 0.04 USD tablet
CVS Pharmacy folic acid 800 mcg tablet 0.02 USD tablet
Folic acid 0.4 mg tablet 0.02 USD tablet
Folic acid 0.8 mg tablet 0.02 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 250 dec °C PhysProp
water solubility 1.6 mg/L (at 25 °C) MERCK INDEX (1983)
logP -2.5 Not Available
Predicted Properties
Property Value Source
water solubility 7.61e-02 g/l ALOGPS
logP -0.04 ALOGPS
logP -0.68 ChemAxon
logS -3.8 ALOGPS
pKa (strongest acidic) 3.37 ChemAxon
pKa (strongest basic) 2.09 ChemAxon
physiological charge -2 ChemAxon
hydrogen acceptor count 12 ChemAxon
hydrogen donor count 6 ChemAxon
polar surface area 208.99 ChemAxon
rotatable bond count 9 ChemAxon
refractivity 111.01 ChemAxon
polarizability 42.06 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Kamen B: Folate and antifolate pharmacology. Semin Oncol. 1997 Oct;24(5 Suppl 18):S18-30-S18-39. Pubmed
  2. Fenech M, Aitken C, Rinaldi J: Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults. Carcinogenesis. 1998 Jul;19(7):1163-71. Pubmed
  3. Zittoun J: [Anemias due to disorder of folate, vitamin B12 and transcobalamin metabolism] Rev Prat. 1993 Jun 1;43(11):1358-63. Pubmed
  4. Alaimo K, McDowell MA, Briefel RR, Bischof AM, Caughman CR, Loria CM, Johnson CL: Dietary intake of vitamins, minerals, and fiber of persons ages 2 months and over in the United States: Third National Health and Nutrition Examination Survey, Phase 1, 1988-91. Adv Data. 1994 Nov 14;(258):1-28. Pubmed
  5. Raiten DJ, Fisher KD: Assessment of folate methodology used in the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). J Nutr. 1995 May;125(5):1371S-1398S. Pubmed
External Links
Resource Link
KEGG Drug D00070 Link_out
KEGG Compound C00504 Link_out
PubChem Compound 6037 Link_out
PubChem Substance 46508092 Link_out
ChemSpider 5815 Link_out
ChEBI 27470 Link_out
ChEMBL 27470 Link_out
Therapeutic Targets Database DAP001309 Link_out
PharmGKB PA449692 Link_out
HET FOL Link_out
Drugs.com http://www.drugs.com/folic_acid.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/fol_0110.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Folic_Acid Link_out
ATC Codes
  • B03BB01
AHFS Codes
  • 88:08.00
PDB Entries
FDA label Not Available
MSDS show (73.7 KB)
Interactions
Drug Interactions
Drug Interaction
Amobarbital Folic acid decreases the effect of anticonvulsant, amobarbital.
Aprobarbital Folic acid decreases the effect of anticonvulsant, aprobarbital.
Butabarbital Folic acid decreases the effect of anticonvulsant, butabarbital.
Butalbital Folic acid decreases the effect of anticonvulsant, butalbital.
Butethal Folic acid decreases the effect of anticonvulsant, butethal.
Dihydroquinidine barbiturate Folic acid decreases the effect of anticonvulsant, dihydroquinidine barbiturate.
Ethotoin Folic acid decreases the levels of hydantoin
Fosphenytoin Folic acid decreases the levels of hydantoin
Heptabarbital Folic acid decreases the effect of anticonvulsant, heptabarbital.
Hexobarbital Folic acid decreases the effect of anticonvulsant, hexobarbital.
Mephenytoin Folic acid decreases the levels of hydantoin
Methohexital Folic acid decreases the effect of anticonvulsant, methohexital.
Methylphenobarbital Folic acid decreases the effect of anticonvulsant, methylphenobarbital.
Pentobarbital Folic acid decreases the effect of anticonvulsant, pentobarbital.
Phenobarbital Folic acid decreases the effect of anticonvulsant, phenobarbital.
Phenytoin Folic acid may decrease the levels of phenytoin.
Primidone Folic acid decreases the effect of anticonvulsant, primidone.
Quinidine barbiturate Folic acid decreases the effect of anticonvulsant, quinidine barbiturate.
Secobarbital Folic acid decreases the effect of anticonvulsant, secobarbital.
Talbutal Folic acid decreases the effect of anticonvulsant, talbutal.
Food Interactions Not Available
Targets

1. Folate receptor beta

Pharmacological action: unknown
Actions: binder

Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate to the interior of cells

Organism class: human
UniProt ID: P14207 Link_out
Gene: FOLR2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Dixit V, Van den Bossche J, Sherman DM, Thompson DH, Andres RP: Synthesis and grafting of thioctic acid-PEG-folate conjugates onto Au nanoparticles for selective targeting of folate receptor-positive tumor cells. Bioconjug Chem. 2006 May-Jun;17(3):603-9. Pubmed
  2. Wlodarczyk BJ, Cabrera RM, Hill DS, Bozinov D, Zhu H, Finnell RH: Arsenic-induced gene expression changes in the neural tube of folate transport defective mouse embryos. Neurotoxicology. 2006 Jul;27(4):547-57. Epub 2006 Apr 18. Pubmed
  3. Boyles AL, Billups AV, Deak KL, Siegel DG, Mehltretter L, Slifer SH, Bassuk AG, Kessler JA, Reed MC, Nijhout HF, George TM, Enterline DS, Gilbert JR, Speer MC: Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions. Environ Health Perspect. 2006 Oct;114(10):1547-52. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Folate receptor gamma

Pharmacological action: unknown
Actions: binder

Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate to the interior of cells. Isoform Short does not bind folate

Organism class: human
UniProt ID: P41439 Link_out
Gene: FOLR3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Shen F, Ross JF, Wang X, Ratnam M: Identification of a novel folate receptor, a truncated receptor, and receptor type beta in hematopoietic cells: cDNA cloning, expression, immunoreactivity, and tissue specificity. Biochemistry. 1994 Feb 8;33(5):1209-15. Pubmed
  4. Shen F, Wu M, Ross JF, Miller D, Ratnam M: Folate receptor type gamma is primarily a secretory protein due to lack of an efficient signal for glycosylphosphatidylinositol modification: protein characterization and cell type specificity. Biochemistry. 1995 Apr 25;34(16):5660-5. Pubmed
  5. Prasad PD, Ramamoorthy S, Moe AJ, Smith CH, Leibach FH, Ganapathy V: Selective expression of the high-affinity isoform of the folate receptor (FR-alpha) in the human placental syncytiotrophoblast and choriocarcinoma cells. Biochim Biophys Acta. 1994 Aug 11;1223(1):71-5. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Enzymes

1. Cytochrome P450 2E1

Actions: substrate

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Gamma-glutamyl hydrolase

Actions: substrate

Hydrolyzes the polyglutamate sidechains of pteroylpolyglutamates. Progressively removes gamma-glutamyl residues from pteroylpoly-gamma-glutamate to yield pteroyl-alpha- glutamate (folic acid) and free glutamate. May play an important role in the bioavailability of dietary pteroylpolyglutamates and in the metabolism of pteroylpolyglutamates and antifolates

UniProt ID: Q92820 Link_out
Gene: GGH Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Schneider E, Ryan TJ: Gamma-glutamyl hydrolase and drug resistance. Clin Chim Acta. 2006 Dec;374(1-2):25-32. Epub 2006 Jun 10. Pubmed
  2. Eisele LE, Chave KJ, Lehning AC, Ryan TJ: Characterization of Human gamma-glutamyl hydrolase in solution demonstrates that the enzyme is a non-dissociating homodimer. Biochim Biophys Acta. 2006 Sep;1764(9):1479-86. Epub 2006 Jul 12. Pubmed
  3. Chen L, Eitenmiller RR: Optimization of the trienzyme extraction for the microbiological assay of folate in vegetables. J Agric Food Chem. 2007 May 16;55(10):3884-8. Epub 2007 Apr 17. Pubmed

3. Methylenetetrahydrofolate reductase

Actions: substrate

Catalyzes the conversion of 5,10- methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co- substrate for homocysteine remethylation to methionine

UniProt ID: P42898 Link_out
Gene: MTHFR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. West AA, Caudill MA: Genetic variation: impact on folate (and choline) bioefficacy. Int J Vitam Nutr Res. 2010 Oct;80(4-5):319-29. Pubmed
  2. Kim YI: Role of the MTHFR polymorphisms in cancer risk modification and treatment. Future Oncol. 2009 May;5(4):523-42. Pubmed
Transporters

1. Canalicular multispecific organic anion transporter 2

Actions: substrate

May act as an inducible transporter in the biliary and intestinal excretion of organic anions

UniProt ID: O15438 Link_out
Gene: ABCC3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

2. ATP-binding cassette transporter sub-family C member 11

Actions: substrate

Participates in physiological processes involving bile acids, conjugated steroids and cyclic nucleotides. Enhances the cellular extrusion of cAMP and cGMP. Stimulates the ATP-dependent uptake of a range of physiological and synthetic lipophilic anions, including the glutathione S-conjugates leukotriene C4 and dinitrophenyl S-glutathione, steroid sulfates such as dehydroepiandrosterone 3-sulfate (DHEAS) and estrone 3-sulfate, glucuronides such as estradiol 17-beta-D-glucuronide (E(2)17betaG), the monoanionic bile acids glycocholate and taurocholate, and methotrexate. Probably functions to secrete earwax

UniProt ID: Q96J66 Link_out
Gene: ABCC11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen ZS, Guo Y, Belinsky MG, Kotova E, Kruh GD: Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol Pharmacol. 2005 Feb;67(2):545-57. Epub 2004 Nov 10. Pubmed

3. Multidrug resistance-associated protein 4

Actions: inhibitor

May be an organic anion pump relevant to cellular detoxification

UniProt ID: O15439 Link_out
Gene: ABCC4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  2. Rius M, Nies AT, Hummel-Eisenbeiss J, Jedlitschky G, Keppler D: Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane. Hepatology. 2003 Aug;38(2):374-84. Pubmed

4. ATP-binding cassette sub-family G member 2

Actions: substrate

Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123

UniProt ID: Q9UNQ0 Link_out
Gene: ABCG2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

5. Heme carrier protein 1

Actions: substrate

Intestinal heme transporter which mediates heme uptake from the gut lumen into duodenal epithelial cells; the iron is then released from heme and may be transported into the bloodstream. Dietary heme iron is an important nutritional source of iron

UniProt ID: Q96NT5 Link_out
Gene: SLC46A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nakai Y, Inoue K, Abe N, Hatakeyama M, Ohta KY, Otagiri M, Hayashi Y, Yuasa H: Functional characterization of human proton-coupled folate transporter/heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter. J Pharmacol Exp Ther. 2007 Aug;322(2):469-76. Epub 2007 May 2. Pubmed
  2. Ashokkumar B, Mohammed ZM, Vaziri ND, Said HM: Effect of folate oversupplementation on folate uptake by human intestinal and renal epithelial cells. Am J Clin Nutr. 2007 Jul;86(1):159-66. Pubmed

6. Mitochondrial folate transporter/carrier

Actions: substrate

Transports folate across the inner membranes of mitochondria

UniProt ID: Q9H2D1 Link_out
Gene: SLC25A32 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

7. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kuze K, Graves P, Leahy A, Wilson P, Stuhlmann H, You G: Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells. J Biol Chem. 1999 Jan 15;274(3):1519-24. Pubmed
  2. Uwai Y, Okuda M, Takami K, Hashimoto Y, Inui K: Functional characterization of the rat multispecific organic anion transporter OAT1 mediating basolateral uptake of anionic drugs in the kidney. FEBS Lett. 1998 Nov 6;438(3):321-4. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19