Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2013-02-09 00:07:55 UTC
HMDB IDHMDB00121
Secondary Accession NumbersNone
Metabolite Identification
Common NameFolic acid
DescriptionFolic acid is 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, being 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, methylated tRNA, and generate and use formate. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.
Structure
Thumb
Synonyms
  1. Acifolic
  2. Cytofol
  3. Dosfolat B activ
  4. Folacid
  5. Folacin
  6. Folate
  7. Folbal
  8. Folcidin
  9. Foldine
  10. Folettes
  11. Foliamin
  12. Folic acid
  13. Folicet
  14. Folipac
  15. Folsan
  16. Folsaure
  17. Folsav
  18. Folvite
  19. Incafolic
  20. Liver Lactobacillus casei factor
  21. Millafol
  22. N-(4-{[(2-Amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino}benzoyl)-L-glutamic acid
  23. N-Pteroyl-L-glutamic acid
  24. N-[(4-{[(2-Amino-4-oxo-1,4-dihydropteridin-6-yl)methyl]amino}phenyl)carbonyl]-L-glutamic acid
  25. N-[4-[[(2-Amino-3,4-dihydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-glutamic acid
  26. PGA
  27. PteGlu
  28. Pteroyl-L-glutamate
  29. Pteroyl-L-glutamic acid
  30. Pteroyl-L-monoglutamate
  31. Pteroyl-L-monoglutamic acid
  32. Pteroylglutamate
  33. Pteroylglutamic acid
  34. Pteroylmonoglutamic acid
  35. Vitamin Bc
  36. Vitamin Be
  37. Vitamin M
Chemical FormulaC19H19N7O6
Average Molecular Weight441.3975
Monoisotopic Molecular Weight441.139681375
IUPAC Name(2S)-2-[(4-{[(2-amino-4-oxo-1,4-dihydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid
Traditional IUPAC Namefolic acid
CAS Registry Number59-30-3
SMILES
NC1=NC(=O)C2=NC(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)=CN=C2N1
InChI Identifier
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
InChI KeyOVBPIULPVIDEAO-LBPRGKRZSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAromatic Heteropolycyclic Compounds
ClassPteridines and Derivatives
Sub ClassPterins and Derivatives
Other Descriptors
  • Aromatic Heteropolycyclic Compounds
  • N-acylamino acid(ChEBI)
  • Water-soluble vitamins(KEGG)
  • folate(ChEBI)
Substituents
  • Alpha Amino Acid Or Derivative
  • Aminobenzamide
  • Aminopyrimidine
  • Benzamide
  • Benzoyl
  • Carboxamide Group
  • Carboxylic Acid
  • Dicarboxylic Acid Derivative
  • Hippurate
  • N Acyl Alpha Amino Acid
  • N Substituted Alpha Amino Acid
  • Polyamine
  • Pteroic Acid Derivative
  • Pyrazine
  • Pyrimidine
  • Pyrimidone
  • Secondary Carboxylic Acid Amide
Direct ParentFolic Acid Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Drug
  • Food
Biofunction
  • Component of Cyanoamino acid metabolism
  • Component of Folate biosynthesis
  • Component of Glycine, serine and threonine metabolism
  • Component of Glyoxylate and dicarboxylate metabolism
  • Component of Methane metabolism
  • Component of Pyrimidine metabolism
  • DNA component
  • Enzyme co-factor
  • Essential vitamins
ApplicationNot Available
Cellular locations
  • Extracellular
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point250 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.0016 mg/mLNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
water solubility0.076 g/LALOGPS
logP-0.04ALOGPS
logP-0.68ChemAxon
logS-3.8ALOGPS
pKa (strongest acidic)3.37ChemAxon
pKa (strongest basic)2.09ChemAxon
physiological charge-2ChemAxon
hydrogen acceptor count12ChemAxon
hydrogen donor count6ChemAxon
polar surface area208.99ChemAxon
rotatable bond count9ChemAxon
refractivity111.01ChemAxon
polarizability42.06ChemAxon
Spectra
Spectra
Biological Properties
Cellular Locations
  • Extracellular
Biofluid Locations
  • Blood
  • Cellular Cytoplasm
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Location
  • Brain
  • Erythrocyte
  • Kidney
  • Liver
Pathways
NameSMPDB LinkKEGG Link
Folate MetabolismSMP00053map00670
Pterine BiosynthesisSMP00005map00790
Normal Concentrations
BiofluidStatusValueAgeSexConditionReference
BloodDetected and Quantified0.021 (0.017-0.025) uMAdult (>18 years old)BothNormal
BloodDetected and Quantified0.039 (0.01 - 0.14) uMNewborn (0-30 days old)Not SpecifiedNormal
  • Geigy Scient...
BloodDetected and Quantified0.011 (0.004 - 0.028) uMChildren (1-13 year old)Not SpecifiedNormal
  • Geigy Scient...
BloodDetected and Quantified0.009 (0.0024 - 0.024) uMAdult (>18 years old)Not SpecifiedNormal
  • Geigy Scient...
BloodDetected and Quantified0.077 (0.071 - 0.083) uMAdult (>18 years old)BothNormal
BloodDetected and Quantified0.02 (0.011- 0.036) uMAdult (>18 years old)BothNormal
  • Wu AHB. Tiet...
BloodDetected and Quantified0.009 (0.0026-0.026) uMAdult (>18 years old)FemaleNormal
  • Geigy Scient...
BloodDetected and Quantified0.023 (0.002-0.045) uMChildren (1-13 year old)BothNormal
Cellular CytoplasmDetected and Quantified0.735 +/- 0.202 uMNewborn (0-30 days old)Not SpecifiedNormal
  • Geigy Scient...
Cellular CytoplasmDetected and Quantified0.453 +/- 0.131 uMAdult (>18 years old)Not SpecifiedNormal
  • Geigy Scient...
Cellular CytoplasmDetected and Quantified> 0.35 uMAdult (>18 years old)BothNormal
Cerebrospinal Fluid (CSF)Detected and Quantified0.0078 +/- 0.0011 uMAdult (>18 years old)Not SpecifiedNormal
Cerebrospinal Fluid (CSF)Detected and Quantified0.053 +/- 0.024 uMAdult (>18 years old)BothNormal
  • Geigy Scient...
Cerebrospinal Fluid (CSF)Detected and Quantified0.006 +/- 0.0005 uMElderly (>65 years old)BothNormal
Cerebrospinal Fluid (CSF)Detected and Quantified0.0202 +/- 0.00567 uMAdult (>18 years old)FemaleNormal
UrineDetected and Quantified0.00065 (0.000092-0.0013) umol/mmol creatinineAdult (>18 years old)FemaleNormal
  • Geigy Scient...
UrineDetected and Quantified0.0014 (0.000013-0.0026) umol/mmol creatinineAdult (>18 years old)BothNormal
  • Geigy Scient...
UrineDetected and Quantified< 0.01 umol/mmol creatinineAdult (>18 years old)BothNormal
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReference
BloodDetected and Quantified0.023 (0.019-0.028) uMAdult (>18 years old)BothCommentRheumatoid arthritis
BloodDetected and Quantified0.023 (0.020-0.026) uMAdult (>18 years old)BothCommentRheumatoid arthritis
BloodDetected and Quantified0.003 (0.0 - 0.007) uMAdult (>18 years old)BothFolate deficiency
  • Wu AHB. Tiet...
Cerebrospinal Fluid (CSF)Detected and Quantified0.0203 +/- 0.0017 uMAdult (>18 years old)Not SpecifiedAlzheimer's disease
Cerebrospinal Fluid (CSF)Detected and Quantified0.0209 +/- 0.00703 uMAdult (>18 years old)Not Specifiedfibromyalgia
Cerebrospinal Fluid (CSF)Detected and Quantified0.008 +/- 0.0011 uMElderly (>65 years old)BothAlzheimer's disease
Cerebrospinal Fluid (CSF)Detected and Quantified0.0056 +/- 0.005 uMAdult (>18 years old)BothAlzheimer's disease
Associated Disorders and Diseases
Disease References
Alzheimer's disease
  • Selley ML, Close DR, Stern SE: The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer's disease. Neurobiol Aging. 2002 May-Jun;23(3):383-8. Pubmed: 11959400
Folate deficiency
  • Wu AHB. Tietz clinical guide to laboratory tests. 4th ed. St. Louis: Saunders/Elsevier. 2006.
Rheumatoid arthritis
  • Chiang EP, Smith DE, Selhub J, Dallal G, Wang YC, Roubenoff R: Inflammation causes tissue-specific depletion of vitamin B6. Arthritis Res Ther. 2005;7(6):R1254-62. Epub 2005 Sep 13. Pubmed: 16277678
Associated OMIM IDs
DrugBank IDDB00158
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB014504
KNApSAcK IDC00001539
Chemspider ID5815
KEGG Compound IDC00504
BioCyc IDFOLATE
BiGG ID35180
Wikipedia LinkFolic acid
NuGOwiki LinkHMDB00121
Metagene LinkHMDB00121
METLIN ID246
PubChem Compound6037
PDB IDFOL
ChEBI ID27470
References
Synthesis ReferencePiper, James R.; McCaleb, George S.; Montgomery, John A. Synthesis of 10-propargylfolic acid from 2-amino-6-(bromomethyl)-4(1H)-pteridinone. Journal of Heterocyclic Chemistry (1987), 24(1), 279-82.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Kopczynska E, Ziolkowski M, Jendryczka-Mackiewicz E, Odrowaz-Sypniewska G, Opozda K, Tyrakowski T: [The concentrations of homocysteine, folic acid and vitamin B12 in alcohol dependent male patients] Psychiatr Pol. 2004 Sep-Oct;38(5):947-56. Pubmed: 15523939
  2. Gregory JF 3rd, Williamson J, Liao JF, Bailey LB, Toth JP: Kinetic model of folate metabolism in nonpregnant women consuming [2H2]folic acid: isotopic labeling of urinary folate and the catabolite para-acetamidobenzoylglutamate indicates slow, intake-dependent, turnover of folate pools. J Nutr. 1998 Nov;128(11):1896-906. Pubmed: 9808640
  3. Lin Y, Dueker SR, Follett JR, Fadel JG, Arjomand A, Schneider PD, Miller JW, Green R, Buchholz BA, Vogel JS, Phair RD, Clifford AJ: Quantitation of in vivo human folate metabolism. Am J Clin Nutr. 2004 Sep;80(3):680-91. Pubmed: 15321809
  4. Rodriguez Flores J, Penalvo GC, Mansilla AE, Gomez MJ: Capillary electrophoretic determination of methotrexate, leucovorin and folic acid in human urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 May 5;819(1):141-7. Pubmed: 15797531
  5. Selley ML, Close DR, Stern SE: The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer's disease. Neurobiol Aging. 2002 May-Jun;23(3):383-8. Pubmed: 11959400
  6. Litwin M, Abuauba M, Wawer ZT, Grenda R, Kuryl T, Pietraszek E: [Sulphur amino acids, vitamin B12 and folic acid in children with chronic renal failure] Pol Merkur Lekarski. 2000 Apr;8(46):268-9. Pubmed: 10897644
  7. Gregory JF 3rd, Williamson J, Bailey LB, Toth JP: Urinary excretion of [2H4]folate by nonpregnant women following a single oral dose of [2H4]folic acid is a functional index of folate nutritional status. J Nutr. 1998 Nov;128(11):1907-12. Pubmed: 9808641
  8. Dietrich M, Brown CJ, Block G: The effect of folate fortification of cereal-grain products on blood folate status, dietary folate intake, and dietary folate sources among adult non-supplement users in the United States. J Am Coll Nutr. 2005 Aug;24(4):266-74. Pubmed: 16093404
  9. Pufulete M, Al-Ghnaniem R, Khushal A, Appleby P, Harris N, Gout S, Emery PW, Sanders TA: Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma. Gut. 2005 May;54(5):648-53. Pubmed: 15831910
  10. Clifford AJ, Arjomand A, Dueker SR, Schneider PD, Buchholz BA, Vogel JS: The dynamics of folic acid metabolism in an adult given a small tracer dose of 14C-folic acid. Adv Exp Med Biol. 1998;445:239-51. Pubmed: 9781393
  11. Olthof MR, Bots ML, Katan MB, Verhoef P: Effect of folic Acid and betaine supplementation on flow-mediated dilation: a randomized, controlled study in healthy volunteers. PLoS Clin Trials. 2006 Jun;1(2):e10. Epub 2006 Jun 9. Pubmed: 16871332
  12. Stern LL, Bagley PJ, Rosenberg IH, Selhub J: Conversion of 5-formyltetrahydrofolic acid to 5-methyltetrahydrofolic acid is unimpaired in folate-adequate persons homozygous for the C677T mutation in the methylenetetrahydrofolate reductase gene. J Nutr. 2000 Sep;130(9):2238-42. Pubmed: 10958818
  13. Stuerenburg HJ, Ganzer S, Arlt S, Muller-Thomsen T: The influence of smoking on plasma folate and lipoproteins in Alzheimer disease, mild cognitive impairment and depression. Neuro Endocrinol Lett. 2005 Jun;26(3):261-3. Pubmed: 15990733
  14. Cahill E, McPartlin J, Gibney MJ: The effects of fasting and refeeding healthy volunteers on serum folate levels. Int J Vitam Nutr Res. 1998;68(2):142-5. Pubmed: 9565830
  15. 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: 7738698
  16. Zittoun J: [Anemias due to disorder of folate, vitamin B12 and transcobalamin metabolism]. Rev Prat. 1993 Jun 1;43(11):1358-63. Pubmed: 8235383
  17. Kamen B: Folate and antifolate pharmacology. Semin Oncol. 1997 Oct;24(5 Suppl 18):S18-30-S18-39. Pubmed: 9420019
  18. 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: 9683174
  19. 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: 10138938

Enzymes

Gene Name:
MTHFR
Uniprot ID:
P42898
Gene Name:
GNMT
Uniprot ID:
Q14749
Gene Name:
DHFR
Uniprot ID:
P00374
Reactions
Tetrahydrofolic acid + NAD unknown Folic acid + NADH + Hydrogen Iondetails
Tetrahydrofolic acid + NADP unknown Folic acid + NADPH + Hydrogen Iondetails
Dihydrofolic acid + NAD unknown Folic acid + NADH + Hydrogen Iondetails
Dihydrofolic acid + NADP unknown Folic acid + NADPH + Hydrogen Iondetails
Gene Name:
CYP2E1
Uniprot ID:
P05181
Gene Name:
FOLR1
Uniprot ID:
P15328
Gene Name:
SLC19A1
Uniprot ID:
P41440
Gene Name:
SLC19A2
Uniprot ID:
O60779
Gene Name:
FOLR3
Uniprot ID:
P41439
Gene Name:
GGH
Uniprot ID:
Q92820
Gene Name:
DYR
Uniprot ID:
B0YJ76
Gene Name:
FOLR2
Uniprot ID:
P14207
Gene Name:
C2orf83
Uniprot ID:
Q53S99
Gene Name:
FOLR4
Uniprot ID:
A6ND01
Gene Name:
DHFRL1
Uniprot ID:
Q86XF0
Reactions
Tetrahydrofolic acid + NAD unknown Folic acid + NADH + Hydrogen Iondetails
Tetrahydrofolic acid + NADP unknown Folic acid + NADPH + Hydrogen Iondetails
Dihydrofolic acid + NAD unknown Folic acid + NADH + Hydrogen Iondetails
Dihydrofolic acid + NADP unknown Folic acid + NADPH + Hydrogen Iondetails

Transporters

Gene Name:
SLC46A1
Uniprot ID:
Q96NT5
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Gene Name:
SLC25A32
Uniprot ID:
Q9H2D1