You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
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 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
SpectraMS/MSLC-MS1D NMR2D NMR
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
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.021 (0.017-0.025) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.039 (0.01 - 0.14) uMNewborn (0-30 days old)Not SpecifiedNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified0.011 (0.004 - 0.028) uMChildren (1-13 years old)Not SpecifiedNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified0.009 (0.0024 - 0.024) uMAdult (>18 years old)Not SpecifiedNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified0.077 (0.071 - 0.083) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.02 (0.011- 0.036) uMAdult (>18 years old)BothNormal
    • Wu AHB. Tietz cli...
details
BloodDetected and Quantified0.009 (0.0026-0.026) uMAdult (>18 years old)FemaleNormal
    • Geigy Scientific ...
details
BloodDetected and Quantified0.023 (0.002-0.045) uMChildren (1-13 years old)BothNormal details
Cellular CytoplasmDetected and Quantified0.735 +/- 0.202 uMNewborn (0-30 days old)Not SpecifiedNormal
    • Geigy Scientific ...
details
Cellular CytoplasmDetected and Quantified0.453 +/- 0.131 uMAdult (>18 years old)Not SpecifiedNormal
    • Geigy Scientific ...
details
Cellular CytoplasmDetected and Quantified> 0.35 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0078 +/- 0.0011 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.053 +/- 0.024 uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
Cerebrospinal Fluid (CSF)Detected and Quantified0.006 +/- 0.0005 uMElderly (>65 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0202 +/- 0.00567 uMAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified0.00065 (0.000092-0.0013) umol/mmol creatinineAdult (>18 years old)FemaleNormal
    • Geigy Scientific ...
details
UrineDetected and Quantified0.0014 (0.000013-0.0026) umol/mmol creatinineAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
UrineDetected and Quantified< 0.01 umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.023 (0.019-0.028) uMAdult (>18 years old)Both
Rheumatoid arthritis
details
BloodDetected and Quantified0.023 (0.020-0.026) uMAdult (>18 years old)Both
Rheumatoid arthritis
details
BloodDetected and Quantified0.003 (0.0 - 0.007) uMAdult (>18 years old)BothFolate deficiency
    • Wu AHB. Tietz cli...
details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0203 +/- 0.0017 uMAdult (>18 years old)Not SpecifiedAlzheimer's disease details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0209 +/- 0.00703 uMAdult (>18 years old)Not Specifiedfibromyalgia details
Cerebrospinal Fluid (CSF)Detected and Quantified0.008 +/- 0.0011 uMElderly (>65 years old)BothAlzheimer's disease details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0056 +/- 0.005 uMAdult (>18 years old)BothAlzheimer's disease details
Associated Disorders and Diseases
Disease References
Alzheimer's disease
  1. 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
  1. Wu AHB. Tietz clinical guide to laboratory tests. 4th ed. St. Louis: Saunders/Elsevier. 2006.
Rheumatoid arthritis
  1. 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)Download (PDF)
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

General function:
Involved in methylenetetrahydrofolate reductase (NADPH) activity
Specific function:
Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine.
Gene Name:
MTHFR
Uniprot ID:
P42898
Molecular weight:
74595.895
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: 21462116
  2. Kim YI: Role of the MTHFR polymorphisms in cancer risk modification and treatment. Future Oncol. 2009 May;5(4):523-42. Pubmed: 19450180
General function:
Involved in folic acid binding
Specific function:
Catalyzes the methylation of glycine by using S-adenosylmethionine (AdoMet) to form N-methylglycine (sarcosine) with the concomitant production of S-adenosylhomocysteine (AdoHcy). Possible crucial role in the regulation of tissue concentration of AdoMet and of metabolism of methionine.
Gene Name:
GNMT
Uniprot ID:
Q14749
Molecular weight:
32742.0
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
General function:
Involved in dihydrofolate reductase activity
Specific function:
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.
Gene Name:
DHFR
Uniprot ID:
P00374
Molecular weight:
21452.61
Reactions
Tetrahydrofolic acid + NAD → Folic acid + NADH + Hydrogen Iondetails
Tetrahydrofolic acid + NADP → Folic acid + NADPH + Hydrogen Iondetails
Dihydrofolic acid + NAD → Folic acid + NADH + Hydrogen Iondetails
Dihydrofolic acid + NADP → Folic acid + NADPH + Hydrogen Iondetails
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
General function:
Involved in monooxygenase activity
Specific function:
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.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular weight:
56848.42
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: 19934256
General function:
Involved in folic acid binding
Specific function:
Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate to the interior of cells
Gene Name:
FOLR1
Uniprot ID:
P15328
Molecular weight:
29818.9
General function:
Involved in folic acid binding
Specific function:
Transporter for the intake of folate. Uptake of folate in human placental choriocarcinoma cells occurs by a novel mechanism called potocytosis which functionally couples three components, namely the folate receptor, the folate transporter, and a V-type H(+)-pump.
Gene Name:
SLC19A1
Uniprot ID:
P41440
Molecular weight:
54261.68
General function:
Involved in folic acid binding
Specific function:
High-affinity transporter for the intake of thiamine.
Gene Name:
SLC19A2
Uniprot ID:
O60779
Molecular weight:
55399.49
General function:
Involved in folic acid binding
Specific function:
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
Gene Name:
FOLR3
Uniprot ID:
P41439
Molecular weight:
27638.0
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: 17139284
  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: 17016423
  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: 8110752
  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: 7727426
  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: 8061055
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed: 11752352
General function:
Involved in catalytic activity
Specific function:
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.
Gene Name:
GGH
Uniprot ID:
Q92820
Molecular weight:
35964.045
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: 16859665
  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: 16945597
  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: 17439143
General function:
Involved in dihydrofolate reductase activity
Specific function:
Not Available
Gene Name:
DYR
Uniprot ID:
B0YJ76
Molecular weight:
21452.6
General function:
Involved in folic acid binding
Specific function:
Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate to the interior of cells
Gene Name:
FOLR2
Uniprot ID:
P14207
Molecular weight:
29279.3
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: 16704197
  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: 16620997
  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: 17035141
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed: 11752352
General function:
Involved in folic acid binding
Specific function:
Not Available
Gene Name:
C2orf83
Uniprot ID:
Q53S99
Molecular weight:
10585.365
General function:
Involved in folic acid binding
Specific function:
Not Available
Gene Name:
FOLR4
Uniprot ID:
A6ND01
Molecular weight:
28132.0
General function:
Not Available
Specific function:
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Required to prevent uracil accumulation in mtDNA. Binds its own mRNA and that of DHFR.
Gene Name:
DHFRL1
Uniprot ID:
Q86XF0
Molecular weight:
21619.88
Reactions
Tetrahydrofolic acid + NAD → Folic acid + NADH + Hydrogen Iondetails
Tetrahydrofolic acid + NADP → Folic acid + NADPH + Hydrogen Iondetails
Dihydrofolic acid + NAD → Folic acid + NADH + Hydrogen Iondetails
Dihydrofolic acid + NADP → Folic acid + NADPH + Hydrogen Iondetails

Transporters

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
General function:
Involved in ATP binding
Specific function:
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
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular weight:
72313.5
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: 12874005
General function:
Involved in transmembrane transport
Specific function:
Has been shown to act both as an intestinal proton- coupled high-affinity folate transporter and as an 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. Shows a higher affinity for folate than heme
Gene Name:
SLC46A1
Uniprot ID:
Q96NT5
Molecular weight:
49770.0
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: 17475902
  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: 17616776
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
  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: 12883481
General function:
Involved in ion transmembrane transporter activity
Specific function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS). Mediates the sodium-independent uptake of p- aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3'-azido- 3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro- phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2- furanpropionate (CMPF), cidofovir, adefovir, 9-(2- phosphonylmethoxyethyl) guanine (PMEG), 9-(2- phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p- chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid. PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular weight:
61815.8
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: 9880528
  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: 9827570
General function:
Involved in ATP binding
Specific function:
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
Gene Name:
ABCC11
Uniprot ID:
Q96J66
Molecular weight:
154299.6
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: 15537867
General function:
Involved in transporter activity
Specific function:
Transports folate across the inner membranes of mitochondria.
Gene Name:
SLC25A32
Uniprot ID:
Q9H2D1
Molecular weight:
35406.83
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: 17139284
  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: 17016423