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Identification
NameAlpha-Linolenic Acid
Accession NumberDB00132  (NUTR00034)
TypeSmall Molecule
GroupsApproved, Nutraceutical
Description

Alpha-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. [Wikipedia]

Structure
Thumb
Synonyms
(9,12,15)-linolenic acid
(9Z,12Z,15Z)-Octadecatrienoic acid
(Z,Z,Z)-9,12,15-octadecatrienoic acid
9-cis,12-cis,15-cis-octadecatrienoic acid
9,12,15-Octadecatrienoic acid
ALA
all-cis-9,12,15-Octadecatrienoic acid
alpha-Linolenic acid
cis-delta(9,12,15)-Octadecatrienoic acid
cis,cis,cis-9,12,15-Octadecatrienoic acid
Linolenic acid
α-linolenic acid
External Identifiers Not Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Flax Seed Oilcapsule500 mgoralNutricorp International2000-04-172006-08-02Canada
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
Folcaps Care OneMidlothian Laboratories
Folcaps Omega-3Midlothian Laboratories
Ultimatecare One NfTrigen Laboratories, Inc.
SaltsNot Available
Categories
UNII0RBV727H71
CAS number463-40-1
WeightAverage: 278.4296
Monoisotopic: 278.224580204
Chemical FormulaC18H30O2
InChI KeyInChIKey=DTOSIQBPPRVQHS-PDBXOOCHSA-N
InChI
InChI=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-
IUPAC Name
(9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid
SMILES
CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O
Taxonomy
DescriptionThis compound 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
ClassLineolic acids and derivatives
Sub ClassNot Available
Direct ParentLineolic acids and derivatives
Alternative Parents
Substituents
  • Octadecanoid
  • Long-chain fatty acid
  • Fatty acyl
  • Fatty acid
  • Unsaturated fatty acid
  • Straight chain fatty acid
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Pharmacology
IndicationFor nutritional supplementation and for treating dietary shortage or imbalance.
PharmacodynamicsAlpha Linolenic Acid (ALA) is an 18-carbon polyunsaturated fatty acid with three double bonds. It is also called an omega-3 fatty acid, and is essential for all mammals. Alpha-linolenic acid (or omega 3 fatty acid) intake can decrease the risk of cardiovascular diseases by 1) preventing arrhythmias that can lead to sudden cardiac death, 2) decreasing the risk of thrombosis (blood clot formation) that can lead to heart attack or stroke, 3) decreasing serum triglyceride levels, 4) slowing the growth of atherosclerotic plaque, 5) improving vascular endothelial function, 6) lowering blood pressure slightly, and 7) decreasing inflammation. ALA deficiencies can lead to visual problems and sensory neuropathy. Scaly and hemorrhagic skin or scalp inflammations may also develop.
Mechanism of actionAlpha 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Alpha Linolenic Acid and Linoleic Acid MetabolismMetabolicSMP00018
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9896
Blood Brain Barrier+0.9314
Caco-2 permeable+0.7735
P-glycoprotein substrateNon-substrate0.6766
P-glycoprotein inhibitor INon-inhibitor0.9499
P-glycoprotein inhibitor IINon-inhibitor0.9025
Renal organic cation transporterNon-inhibitor0.9311
CYP450 2C9 substrateNon-substrate0.7735
CYP450 2D6 substrateNon-substrate0.9081
CYP450 3A4 substrateNon-substrate0.6884
CYP450 1A2 substrateInhibitor0.6915
CYP450 2C9 inhibitorNon-inhibitor0.8798
CYP450 2D6 inhibitorNon-inhibitor0.9631
CYP450 2C19 inhibitorNon-inhibitor0.9638
CYP450 3A4 inhibitorNon-inhibitor0.9465
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9426
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.6502
BiodegradationReady biodegradable0.7808
Rat acute toxicity1.4499 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8818
hERG inhibition (predictor II)Non-inhibitor0.9315
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Capsuleoral500 mg
Capsule, gelatin coatedoral
Capsuleoral
Prices
Unit descriptionCostUnit
Alpha lipoic acid 200 mg tablet0.22USD tablet
Alpha-lipoic acid 50 mg caplet0.12USD caplet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateLiquid
Experimental Properties
PropertyValueSource
melting point-16.5 °CPhysProp
boiling point231 °C at 1.70E+01 mm HgPhysProp
water solubility0.000124 mg/mL at 25 °CMEYLAN,WM et al. (1996)
logP6.46SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility0.000266 mg/mLALOGPS
logP6.62ALOGPS
logP6.06ChemAxon
logS-6ALOGPS
pKa (Strongest Acidic)4.99ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity89.64 m3·mol-1ChemAxon
Polarizability34.98 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (10.9 KB)
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (1 TMS)splash10-uz10000000-8765cf82603feb1b448fView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (1 TMS)splash10-zd00000000-302519a616eaed5fcc59View in MoNA
GC-MSGC-MS Spectrum - GC-MS (1 TMS)splash10-zw21000000-2d44b3c70e2992b9a812View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, N/A (Annotated)splash10-04z0000000-aee97e9ea2c7f0783adfView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, N/A (Annotated)splash10-zm00000000-fb92aefc701027239359View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, N/A (Annotated)splash10-z700000000-a5dddfe6f629d1371facView in MoNA
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
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.

US5002767
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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:10775263 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSDownload (19 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
ligand
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...
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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:10765977 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
ligand
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...
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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:21210105 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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 r...
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. [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. 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. [PubMed:17059813 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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 in...
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. [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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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 ...
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. [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 ]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Transporter activity
Specific Function:
B-FABP could be involved in the transport of a so far unknown hydrophobic ligand with potential morphogenic activity during CNS development. It is required for the establishment of the radial glial fiber system in developing brain, a system that is necessary for the migration of immature neurons to establish cortical layers (By similarity).
Gene Name:
FABP7
Uniprot ID:
O15540
Molecular Weight:
14888.855 Da
References
  1. Balendiran GK, Schnutgen F, Scapin G, Borchers T, Xhong N, Lim K, Godbout R, Spener F, Sacchettini JC: Crystal structure and thermodynamic analysis of human brain fatty acid-binding protein. J Biol Chem. 2000 Sep 1;275(35):27045-54. [PubMed:10854433 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on April 25, 2016 14:10