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Record Information
Version2.0
Creation Date2014-09-11 05:17:40 UTC
Update Date2014-12-24 20:26:57 UTC
Accession NumberT3D4812
Identification
Common NameAlpha-Linolenic Acid
ClassSmall Molecule
DescriptionAlpha-linolenic acid (ALA) is a polyunsaturated omega-3 fatty acid. It is a component of many common vegetable oils and is important to human nutrition.
Compound Type
  • Animal Toxin
  • Dietary Supplement
  • Drug
  • Food Toxin
  • Household Toxin
  • Metabolite
  • Micronutrient
  • Natural Compound
  • Nutraceutical
  • Organic Compound
  • Supplement
Chemical Structure
Thumb
Synonyms
Synonym
(9,12,15)-linolenate
(9,12,15)-linolenic acid
(9Z,12Z,15Z)-Octadecatrienoate
(9Z,12Z,15Z)-Octadecatrienoic acid
(Z,Z,Z)-9,12,15-Octadecatrienoate
(Z,Z,Z)-9,12,15-Octadecatrienoic acid
9,12,15-Octadecatrienoate
9,12,15-Octadecatrienoic acid
9-cis,12-cis,15-cis-Octadecatrienoate
9-cis,12-cis,15-cis-Octadecatrienoic acid
a-Linolenate
a-Linolenic acid
ALA
All-cis-9,12,15-Octadecatrienoate
All-cis-9,12,15-Octadecatrienoic acid
alpha-Linolenate
alpha-Linolenic acid
cis,cis,cis-9,12,15-Octadecatrienoate
cis,cis,cis-9,12,15-Octadecatrienoic acid
cis-9,12,15-Octadecatrienoate
cis-9,12,15-Octadecatrienoic acid
cis-delta(9,12,15)-Octadecatrienoic acid
Industrene 120
Linolenate
Linolenic acid
α-Linolenate
α-Linolenic acid
α-linolenic acid
Chemical FormulaC18H30O2
Average Molecular Mass278.430 g/mol
Monoisotopic Mass278.225 g/mol
CAS Registry Number463-40-1
IUPAC Name(9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid
Traditional Nameα linolenic acid
SMILES[H]\C(CC)=C(/[H])C\C([H])=C(\[H])C\C([H])=C(\[H])CCCCCCCC(O)=O
InChI IdentifierInChI=1S/C18H30O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20/h3-4,6-7,9-10H,2,5,8,11-17H2,1H3,(H,19,20)/b4-3-,7-6-,10-9-
InChI KeyInChIKey=DTOSIQBPPRVQHS-PDBXOOCHSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as lineolic acids and derivatives. These are derivatives of lineolic acid. Lineolic acid is a polyunsaturated omega-6 18 carbon long fatty acid, with two CC double bonds at the 9- and 12-positions.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassLineolic acids and derivatives
Direct ParentLineolic acids and derivatives
Alternative Parents
Substituents
  • Octadecanoid
  • Long-chain fatty acid
  • Fatty acid
  • Unsaturated fatty acid
  • Straight chain fatty acid
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Adipose Tissue
  • Epidermis
  • Fibroblasts
  • Intestine
  • Muscle
  • Nervous Tissues
  • Placenta
  • Platelet
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
Alpha Linolenic Acid and Linoleic Acid MetabolismSMP00018 map00592
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceNot Available
Experimental Properties
PropertyValue
Melting Point-16.5°C
Boiling Point231°C at 1.70E+01 mm Hg
Solubility0.000124 mg/mL at 25°C
LogP6.46
Predicted Properties
PropertyValueSource
Water Solubility0.00027 g/LALOGPS
logP6.62ALOGPS
logP6.06ChemAxon
logS-6ALOGPS
pKa (Strongest Acidic)4.99ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 ŲChemAxon
Rotatable Bond Count13ChemAxon
Refractivity89.64 m³·mol⁻¹ChemAxon
Polarizability34.98 ųChemAxon
Number of Rings0ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (1 TMS)splash10-052f-7900000000-8765cf82603feb1b448fJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (1 TMS)splash10-004i-9300000000-302519a616eaed5fcc59JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (1 TMS)splash10-005c-9800000000-2d44b3c70e2992b9a812JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-052f-7900000000-8765cf82603feb1b448fJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-004i-9300000000-302519a616eaed5fcc59JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-005c-9800000000-2d44b3c70e2992b9a812JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-052f-5900000000-28710ea35f196c595e03JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-052e-6950000000-27037263e74c8119ead0JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00ds-6931000000-657fa0cc66a206a36409JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, N/A (Annotated)splash10-004i-0190000000-aee97e9ea2c7f0783adfJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, N/A (Annotated)splash10-05nb-9500000000-fb92aefc701027239359JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, N/A (Annotated)splash10-0aru-9100000000-a5dddfe6f629d1371facJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-TOF 10V, Negativesplash10-004i-0090000000-2b7bea03a685454dd135JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-TOF , Negativesplash10-004i-0090000000-53ddfaed6ce13c37d957JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-TOF 20V, Negativesplash10-004i-0090000000-e5350a66361bc63d1071JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-TOF 30V, Negativesplash10-004i-0090000000-5731aa5e301022c06813JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - ESI-TOF 10V, Negativesplash10-004i-0091010000-6922411e48d747e592b5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT , negativesplash10-001i-0090000000-a18b573ad888d048efa6JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-TOF , negativesplash10-004i-0090000000-2b7bea03a685454dd135JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-TOF , negativesplash10-004i-0090000000-e5350a66361bc63d1071JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-TOF , negativesplash10-004i-0090000000-5731aa5e301022c06813JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF 10V, positivesplash10-004i-0090000000-1d391027db3704d71cb9JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF 20V, positivesplash10-00lr-9210000000-41acd8a55f52afec6d79JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF 40V, positivesplash10-014i-9000000000-a976b4a80a07eb2c4641JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9100000000-497eddf5d738a45f83fbJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 10V, Negativesplash10-004i-0090000000-0c00ca98901526cb2e26JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-004i-1090000000-35ffce9343fe0d15ea0dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-004i-0090000000-373584fbab950d6676ccJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-01t9-0090000000-ae1f482177d0e208165eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00o0-5690000000-20804c8382f14ff0ccf4JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014l-8930000000-9d5e342b1351adc71c20JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0090000000-4d3e8d1180800a7b4ed5JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0059-1090000000-67ab14c068a142dd3c30JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9230000000-403c610d63380e63109aJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityAlpha Linolenic Acid or ALA is considered an essential fatty acid because it is required for human health, but cannot be synthesized by humans. It is in fact a plant-derived fatty acid. Humans can synthesize other omega-3 fatty acids from ALA, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA is a precursor of the series-3 prostaglandins, the series-5 leukotrienes and the series-3 thromboxanes. These eicosanoids have anti-inflammatory and anti-atherogenic properties. ALA metabolites may also inhibit the production of the pro-inflammatory eicosanoids, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), as well as the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). Omega-3 fatty acids like ALA and its byproducts can modulate the expression of a number of genes, including those involved with fatty acid metabolism and inflammation. They regulate gene expression through their effects on the activity of transcription factors including NF-kappa B and members of the peroxisome proliferator-activated receptor (PPAR) family. Incorporation of ALA and its metabolites in cell membranes can affect membrane fluidity and may play a role in anti-inflammatory activity, inhibition of platelet aggregation and possibly in anti-proliferative actions of ALA. ALA is first metabolized by delta6 desaturease into steridonic acid.
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not listed by IARC.
Uses/SourcesFor nutritional supplementation and for treating dietary shortage or imbalance.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00132
HMDB IDHMDB01388
PubChem Compound ID5280934
ChEMBL IDCHEMBL8739
ChemSpider ID4444437
KEGG IDC06427
UniProt IDNot Available
OMIM ID
ChEBI ID27432
BioCyc IDLINOLENIC_ACID
CTD IDD017962
Stitch IDNot Available
PDB IDLNL
ACToR IDNot Available
Wikipedia LinkAlpha-linolenic_acid
References
Synthesis Reference

Jean-Pierre Masse, “Therapeutic composition containing alpha-linolenic acid and a compound capable of promoting the passage of the acid through the cell membrane, plant extract comprising the acid and the compound, and process for the preparation of the extract.” U.S. Patent US5002767, issued February, 1986.

MSDSLink
General References
  1. Kris-Etherton PM, Harris WS, Appel LJ: Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002 Nov 19;106(21):2747-57. [12438303 ]
  2. Connor WE: Importance of n-3 fatty acids in health and disease. Am J Clin Nutr. 2000 Jan;71(1 Suppl):171S-5S. [10617967 ]
  3. Brouwer IA, Katan MB, Zock PL: Dietary alpha-linolenic acid is associated with reduced risk of fatal coronary heart disease, but increased prostate cancer risk: a meta-analysis. J Nutr. 2004 Apr;134(4):919-22. [15051847 ]
  4. Cho E, Hung S, Willett WC, Spiegelman D, Rimm EB, Seddon JM, Colditz GA, Hankinson SE: Prospective study of dietary fat and the risk of age-related macular degeneration. Am J Clin Nutr. 2001 Feb;73(2):209-18. [11157315 ]
  5. Lauritzen I, Blondeau N, Heurteaux C, Widmann C, Romey G, Lazdunski M: Polyunsaturated fatty acids are potent neuroprotectors. EMBO J. 2000 Apr 17;19(8):1784-93. [10775263 ]
  6. Christensen JH, Fabrin K, Borup K, Barber N, Poulsen J: Prostate tissue and leukocyte levels of n-3 polyunsaturated fatty acids in men with benign prostate hyperplasia or prostate cancer. BJU Int. 2006 Feb;97(2):270-3. [16430627 ]
  7. Attar-Bashi NM, Frauman AG, Sinclair AJ: Alpha-linolenic acid and the risk of prostate cancer. What is the evidence? J Urol. 2004 Apr;171(4):1402-7. [15017185 ]
  8. Rastogi SK, Singh J: Effect of chemical penetration enhancer and iontophoresis on the in vitro percutaneous absorption enhancement of insulin through porcine epidermis. Pharm Dev Technol. 2005;10(1):97-104. [15776817 ]
  9. Allman MA, Pena MM, Pang D: Supplementation with flaxseed oil versus sunflowerseed oil in healthy young men consuming a low fat diet: effects on platelet composition and function. Eur J Clin Nutr. 1995 Mar;49(3):169-78. [7774533 ]
  10. Fokkema MR, Brouwer DA, Hasperhoven MB, Martini IA, Muskiet FA: Short-term supplementation of low-dose gamma-linolenic acid (GLA), alpha-linolenic acid (ALA), or GLA plus ALA does not augment LCP omega 3 status of Dutch vegans to an appreciable extent. Prostaglandins Leukot Essent Fatty Acids. 2000 Nov;63(5):287-92. [11090255 ]
  11. Becker CC, Lund P, Holmer G, Jensen H, Sandstrom B: Effects of butter oil blends with increased concentrations of stearic, oleic and linolenic acid on blood lipids in young adults. Eur J Clin Nutr. 1999 Jul;53(7):535-41. [10452408 ]
  12. Jones DB, Scaretto L, Carter R, Mann JI: Glucose, insulin and platelet fatty acids following myocardial infarction: an association with infarct size. Diabete Metab. 1987 Jul-Aug;13(4):463-6. [3315767 ]
  13. Crastes de Paulet A, Babin F, Billeaud C, Bougle D, Sarda P, Mendy F: [Biological effects on premature neonates of a milk formula enriched with alpha-linolenic acid: a multicenter study]. Bull Acad Natl Med. 1994 Feb;178(2):267-73; discussion 273-8. [7913655 ]
  14. Richieri GV, Ogata RT, Kleinfeld AM: Equilibrium constants for the binding of fatty acids with fatty acid-binding proteins from adipocyte, intestine, heart, and liver measured with the fluorescent probe ADIFAB. J Biol Chem. 1994 Sep 30;269(39):23918-30. [7929039 ]
  15. Li D, Sinclair A, Wilson A, Nakkote S, Kelly F, Abedin L, Mann N, Turner A: Effect of dietary alpha-linolenic acid on thrombotic risk factors in vegetarian men. Am J Clin Nutr. 1999 May;69(5):872-82. [10232625 ]
  16. Bhatia KS, Singh J: Effect of linolenic acid/ethanol or limonene/ethanol and iontophoresis on the in vitro percutaneous absorption of LHRH and ultrastructure of human epidermis. Int J Pharm. 1999 Apr 15;180(2):235-50. [10370194 ]
  17. Baylin A, Kabagambe EK, Ascherio A, Spiegelman D, Campos H: Adipose tissue alpha-linolenic acid and nonfatal acute myocardial infarction in Costa Rica. Circulation. 2003 Apr 1;107(12):1586-91. Epub 2003 Mar 10. [12668490 ]
  18. Williard DE, Nwankwo JO, Kaduce TL, Harmon SD, Irons M, Moser HW, Raymond GV, Spector AA: Identification of a fatty acid delta6-desaturase deficiency in human skin fibroblasts. J Lipid Res. 2001 Apr;42(4):501-8. [11290821 ]
  19. Campbell FM, Gordon MJ, Dutta-Roy AK: Preferential uptake of long chain polyunsaturated fatty acids by isolated human placental membranes. Mol Cell Biochem. 1996 Feb 9;155(1):77-83. [8717442 ]
  20. Cunnane SC, Hamadeh MJ, Liede AC, Thompson LU, Wolever TM, Jenkins DJ: Nutritional attributes of traditional flaxseed in healthy young adults. Am J Clin Nutr. 1995 Jan;61(1):62-8. [7825540 ]
  21. Bajaj M, Suraamornkul S, Romanelli A, Cline GW, Mandarino LJ, Shulman GI, DeFronzo RA: Effect of a sustained reduction in plasma free fatty acid concentration on intramuscular long-chain fatty Acyl-CoAs and insulin action in type 2 diabetic patients. Diabetes. 2005 Nov;54(11):3148-53. [16249438 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Stearoyl-coa 9-desaturase activity
Specific Function:
Component of a lipid metabolic pathway that catalyzes biosynthesis of highly unsaturated fatty acids (HUFA) from precursor essential polyunsaturated fatty acids (PUFA) linoleic acid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3). Catalyzes the first and rate limiting step in this pathway which is the desaturation of LA (18:2n-6) and ALA (18:3n-3) into gamma-linoleic acid (GLA) (18:3n-6) and stearidonic acid (18:4n-3) respectively and other desaturation steps. Highly unsaturated fatty acids (HUFA) play pivotal roles in many biological functions. It catalizes as well the introduction of a cis double bond in palmitate to produce the mono-unsaturated fatty acid sapienate, the most abundant fatty acid in sebum.
Gene Name:
FADS2
Uniprot ID:
O95864
Molecular Weight:
52259.075 Da
References
  1. Portolesi R, Powell BC, Gibson RA: Competition between 24:5n-3 and ALA for Delta 6 desaturase may limit the accumulation of DHA in HepG2 cell membranes. J Lipid Res. 2007 Jul;48(7):1592-8. Epub 2007 Apr 4. [17409318 ]
  2. Xiang M, Rahman MA, Ai H, Li X, Harbige LS: Diet and gene expression: delta-5 and delta-6 desaturases in healthy Chinese and European subjects. Ann Nutr Metab. 2006;50(6):492-8. Epub 2006 Sep 19. [16988497 ]
  3. Baylin A, Ruiz-Narvaez E, Kraft P, Campos H: alpha-Linolenic acid, Delta6-desaturase gene polymorphism, and the risk of nonfatal myocardial infarction. Am J Clin Nutr. 2007 Feb;85(2):554-60. [17284757 ]
  4. Li MC, Bu YP, Wang GK, Hu GW, Xing LJ: [Heteologous expression of Mortierella isabellina delta6 -fatty acid desaturase gene in soybean]. Yi Chuan Xue Bao. 2004 Aug;31(8):858-63. [15481543 ]
  5. Ge L, Gordon JS, Hsuan C, Stenn K, Prouty SM: Identification of the delta-6 desaturase of human sebaceous glands: expression and enzyme activity. J Invest Dermatol. 2003 May;120(5):707-14. [12713571 ]
  6. Tan L, Meesapyodsuk D, Qiu X: Molecular analysis of 6 desaturase and 6 elongase from Conidiobolus obscurus in the biosynthesis of eicosatetraenoic acid, a omega3 fatty acid with nutraceutical potentials. Appl Microbiol Biotechnol. 2011 Apr;90(2):591-601. doi: 10.1007/s00253-010-3060-y. Epub 2011 Jan 6. [21210105 ]
General Function:
Oxidoreductase activity
Specific Function:
Isoform 2 does not exhibit any catalytic activity toward 20:3n-6, but it may enhance FADS2 activity (By similarity). Isoform 1 is a component of a lipid metabolic pathway that catalyzes biosynthesis of highly unsaturated fatty acids (HUFA) from precursor essential polyunsaturated fatty acids (PUFA) linoleic acid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3). Catalyzes the desaturation of dihomo-gamma-linoleic acid (DHGLA) (20:3n-6) and eicosatetraenoic acid (20:4n-3) to generate arachidonic acid (AA) (20:4n-6) and eicosapentaenoic acid (EPA)(20:5n-3), respectively.
Gene Name:
FADS1
Uniprot ID:
O60427
Molecular Weight:
51963.945 Da
References
  1. Xiang M, Rahman MA, Ai H, Li X, Harbige LS: Diet and gene expression: delta-5 and delta-6 desaturases in healthy Chinese and European subjects. Ann Nutr Metab. 2006;50(6):492-8. Epub 2006 Sep 19. [16988497 ]
  2. Descomps B, Rodriguez A: [Essential fatty acids and prematurity: a triple experimental approach]. C R Seances Soc Biol Fil. 1995;189(5):781-96. [8673626 ]
  3. Hoffman DR, DeMar JC, Heird WC, Birch DG, Anderson RE: Impaired synthesis of DHA in patients with X-linked retinitis pigmentosa. J Lipid Res. 2001 Sep;42(9):1395-401. [11518758 ]
  4. Maniongui C, Blond JP, Ulmann L, Durand G, Poisson JP, Bezard J: Age-related changes in delta 6 and delta 5 desaturase activities in rat liver microsomes. Lipids. 1993 Apr;28(4):291-7. [8487621 ]
  5. Mohan IK, Das UN: Effect of L-arginine-nitric oxide system on the metabolism of essential fatty acids in chemical-induced diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids. 2000 Jan;62(1):35-46. [10765977 ]
General Function:
Ion channel binding
Specific Function:
Mediates the exchange of one Ca(2+) ion against three to four Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes (PubMed:1374913, PubMed:11241183, PubMed:1476165). Contributes to Ca(2+) transport during excitation-contraction coupling in muscle. In a first phase, voltage-gated channels mediate the rapid increase of cytoplasmic Ca(2+) levels due to release of Ca(2+) stores from the endoplasmic reticulum. SLC8A1 mediates the export of Ca(2+) from the cell during the next phase, so that cytoplasmic Ca(2+) levels rapidly return to baseline. Required for normal embryonic heart development and the onset of heart contractions.
Gene Name:
SLC8A1
Uniprot ID:
P32418
Molecular Weight:
108546.06 Da
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. [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. [17016423 ]
  3. Ander BP, Hurtado C, Raposo CS, Maddaford TG, Deniset JF, Hryshko LV, Pierce GN, Lukas A: Differential sensitivities of the NCX1.1 and NCX1.3 isoforms of the Na+-Ca2+ exchanger to alpha-linolenic acid. Cardiovasc Res. 2007 Jan 15;73(2):395-403. Epub 2006 Sep 23. [17059813 ]
General Function:
Transferase activity
Specific Function:
Catalyzes the first and rate-limiting reaction of the four that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. Condensing enzyme that specifically elongates C24:0 and C26:0 acyl-CoAs. May participate to the production of saturated and monounsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. May play a critical role in early brain and skin development.
Gene Name:
ELOVL4
Uniprot ID:
Q9GZR5
Molecular Weight:
36828.905 Da
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. [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. [17016423 ]
General Function:
Zinc ion binding
Specific Function:
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2.
Gene Name:
PPARA
Uniprot ID:
Q07869
Molecular Weight:
52224.595 Da
References
  1. Murakami K, Ide T, Suzuki M, Mochizuki T, Kadowaki T: Evidence for direct binding of fatty acids and eicosanoids to human peroxisome proliferators-activated receptor alpha. Biochem Biophys Res Commun. 1999 Jul 14;260(3):609-13. [10403814 ]
  2. Vanden Heuvel JP, Thompson JT, Frame SR, Gillies PJ: Differential activation of nuclear receptors by perfluorinated fatty acid analogs and natural fatty acids: a comparison of human, mouse, and rat peroxisome proliferator-activated receptor-alpha, -beta, and -gamma, liver X receptor-beta, and retinoid X receptor-alpha. Toxicol Sci. 2006 Aug;92(2):476-89. Epub 2006 May 26. [16731579 ]
General Function:
Transmembrane signaling receptor activity
Specific Function:
Ligand-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. Involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL. Can be activated by endogenous compounds, including 12-hydroperoxytetraenoic acid and bradykinin. Acts as ionotropic endocannabinoid receptor with central neuromodulatory effects. Triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamine in the hippocampus and nucleus accumbens by affecting AMPA receptors endocytosis (By similarity). Activation by vanilloids, like capsaicin, and temperatures higher than 42 degrees Celsius, exhibits a time- and Ca(2+)-dependent outward rectification, followed by a long-lasting refractory state. Mild extracellular acidic pH (6.5) potentiates channel activation by noxious heat and vanilloids, whereas acidic conditions (pH <6) directly activate the channel.
Gene Name:
TRPV1
Uniprot ID:
Q8NER1
Molecular Weight:
94955.33 Da
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. [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. [17016423 ]
General Function:
Zinc ion binding
Specific Function:
Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.
Gene Name:
NR1H4
Uniprot ID:
Q96RI1
Molecular Weight:
55913.915 Da
References
  1. Zhao A, Yu J, Lew JL, Huang L, Wright SD, Cui J: Polyunsaturated fatty acids are FXR ligands and differentially regulate expression of FXR targets. DNA Cell Biol. 2004 Aug;23(8):519-26. [15307955 ]
General Function:
Zinc ion binding
Specific Function:
Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the acyl-CoA oxidase gene. Decreases expression of NPC1L1 once activated by a ligand.
Gene Name:
PPARD
Uniprot ID:
Q03181
Molecular Weight:
49902.99 Da
References
  1. Vanden Heuvel JP, Thompson JT, Frame SR, Gillies PJ: Differential activation of nuclear receptors by perfluorinated fatty acid analogs and natural fatty acids: a comparison of human, mouse, and rat peroxisome proliferator-activated receptor-alpha, -beta, and -gamma, liver X receptor-beta, and retinoid X receptor-alpha. Toxicol Sci. 2006 Aug;92(2):476-89. Epub 2006 May 26. [16731579 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
Gene Name:
PPARG
Uniprot ID:
P37231
Molecular Weight:
57619.58 Da
References
  1. Vanden Heuvel JP, Thompson JT, Frame SR, Gillies PJ: Differential activation of nuclear receptors by perfluorinated fatty acid analogs and natural fatty acids: a comparison of human, mouse, and rat peroxisome proliferator-activated receptor-alpha, -beta, and -gamma, liver X receptor-beta, and retinoid X receptor-alpha. Toxicol Sci. 2006 Aug;92(2):476-89. Epub 2006 May 26. [16731579 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.35 uMNVS_NR_hPXRNovascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC509.55 uMOT_ERa_EREGFP_0120Odyssey Thera
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. RXRA serves as a common heterodimeric partner for a number of nuclear receptors. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes.
Gene Name:
RXRA
Uniprot ID:
P19793
Molecular Weight:
50810.835 Da
References
  1. Vanden Heuvel JP, Thompson JT, Frame SR, Gillies PJ: Differential activation of nuclear receptors by perfluorinated fatty acid analogs and natural fatty acids: a comparison of human, mouse, and rat peroxisome proliferator-activated receptor-alpha, -beta, and -gamma, liver X receptor-beta, and retinoid X receptor-alpha. Toxicol Sci. 2006 Aug;92(2):476-89. Epub 2006 May 26. [16731579 ]