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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
SynonymLanguageCode
(9,12,15)-linolenic acidNot AvailableNot Available
(9Z,12Z,15Z)-Octadecatrienoic acidNot AvailableNot Available
(Z,Z,Z)-9,12,15-octadecatrienoic acidNot AvailableNot Available
9-cis,12-cis,15-cis-octadecatrienoic acidNot AvailableNot Available
9,12,15-Octadecatrienoic acidNot AvailableNot Available
ALANot AvailableNot Available
all-cis-9,12,15-Octadecatrienoic acidNot AvailableNot Available
alpha-Linolenic acidNot AvailableNot Available
cis-delta(9,12,15)-Octadecatrienoic acidNot AvailableNot Available
cis,cis,cis-9,12,15-Octadecatrienoic acidNot AvailableNot Available
Linolenic acidNot AvailableNot Available
α-linolenic acidNot AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
Categories
CAS number463-40-1
WeightAverage: 278.4296
Monoisotopic: 278.224580204
Chemical FormulaC18H30O2
InChI KeyDTOSIQBPPRVQHS-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
Mass Specshow(10.9 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassLineolic Acids and Derivatives
SubclassNot Available
Direct parentLineolic Acids and Derivatives
Alternative parentsUnsaturated Fatty Acids; Straight Chain Fatty Acids; Polyamines; Enolates; Carboxylic Acids
Substituentsenolate; polyamine; carboxylic acid; carboxylic acid derivative
Classification descriptionThis compound belongs to the lineolic acids and derivatives. These are derivatives of lineolic acid.
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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
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
Property Value Probability
Human Intestinal Absorption + 0.9896
Blood Brain Barrier + 0.9314
Caco-2 permeable + 0.7735
P-glycoprotein substrate Non-substrate 0.6766
P-glycoprotein inhibitor I Non-inhibitor 0.9499
P-glycoprotein inhibitor II Non-inhibitor 0.9025
Renal organic cation transporter Non-inhibitor 0.9311
CYP450 2C9 substrate Non-substrate 0.7735
CYP450 2D6 substrate Non-substrate 0.9081
CYP450 3A4 substrate Non-substrate 0.6884
CYP450 1A2 substrate Inhibitor 0.6915
CYP450 2C9 substrate Non-inhibitor 0.8798
CYP450 2D6 substrate Non-inhibitor 0.9631
CYP450 2C19 substrate Non-inhibitor 0.9638
CYP450 3A4 substrate Non-inhibitor 0.9465
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9426
Ames test Non AMES toxic 0.9132
Carcinogenicity Non-carcinogens 0.6502
Biodegradation Ready biodegradable 0.7808
Rat acute toxicity 1.4499 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8818
hERG inhibition (predictor II) Non-inhibitor 0.9315
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
Prices
Unit descriptionCostUnit
Alpha lipoic acid 200 mg tablet0.22USDtablet
Alpha-lipoic acid 50 mg caplet0.12USDcaplet
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 solubility2.66e-04 g/lALOGPS
logP6.62ALOGPS
logP6.06ChemAxon
logS-6ALOGPS
pKa (strongest acidic)4.99ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count1ChemAxon
polar surface area37.3ChemAxon
rotatable bond count13ChemAxon
refractivity89.64ChemAxon
polarizability34.98ChemAxon
number of rings0ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraGC-MSMS/MS1D NMR2D NMR
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 Reference
  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
  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
  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
  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
  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
External Links
ResourceLink
KEGG CompoundC06427
PubChem Compound5280934
PubChem Substance46507620
ChemSpider4444437
ChEBI27432
ChEMBLCHEMBL8739
PharmGKBPA449384
IUPHAR1049
Guide to Pharmacology1049
HETLNL
WikipediaAlpha-linolenic_acid
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSshow(19 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Fatty acid desaturase 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: ligand

Components

Name UniProt ID Details
Fatty acid desaturase 1 O60427 Details

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
  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
  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
  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
  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

2. Fatty acid desaturase 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: ligand

Components

Name UniProt ID Details
Fatty acid desaturase 2 O95864 Details

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
  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
  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
  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
  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
  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 Jan 6. Pubmed

3. Sodium/calcium exchanger 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Sodium/calcium exchanger 1 P32418 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. 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

4. Transient receptor potential cation channel subfamily V member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Transient receptor potential cation channel subfamily V member 1 Q8NER1 Details

References:

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

5. Elongation of very long chain fatty acids protein 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Elongation of very long chain fatty acids protein 4 Q9GZR5 Details

References:

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

Carriers

1. Fatty acid-binding protein, brain

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Fatty acid-binding protein, brain O15540 Details

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

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Drug created on June 13, 2005 07:24 / Updated on September 24, 2013 10:31