γ-Linolenic acid

**γ-Linolenic acid**
Names
	Preferred IUPAC name (6Z,9Z,12Z)-Octadeca-6,9,12-trienoic acid
	Other names Gamma-linolenic acid, gamolenic acid, GLA
Identifiers
CAS Number	506-26-3 ;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:28661 ;
ChEMBL	ChEMBL464982 ;
ChemSpider	4444436 ;
ECHA InfoCard	100.107.263
IUPHAR/BPS	4710;
PubChem CID	5280933;
UNII	78YC2MAX4O ;
CompTox Dashboard (EPA)	DTXSID7046170 ;
	InChI InChI=1S/C18H30O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20/h6-7,9-10,12-13H,2-5,8,11,14-17H2,1H3,(H,19,20)/b7-6-,10-9-,13-12- Key: VZCCETWTMQHEPK-QNEBEIHSSA-N ; InChI=1/C18H30O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20/h6-7,9-10,12-13H,2-5,8,11,14-17H2,1H3,(H,19,20)/b7-6-,10-9-,13-12- Key: VZCCETWTMQHEPK-QNEBEIHSBP;
	SMILES O=C(O)CCCC\C=C/C\C=C/C\C=C/CCCCC;
Properties
Chemical formula	C18H30O2
Molar mass	278.436 g·mol−1
Appearance	Colorless oil
Pharmacology
ATC code	D11AX02 (WHO)
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

γ-Linolenic acid or GLA (INN: gamolenic acid) is an n−6, or omega-6, fatty acid found primarily in seed oils. When acting on GLA, arachidonate 5-lipoxygenase produces no leukotrienes and the conversion by the enzyme of arachidonic acid to leukotrienes is inhibited.

Chemistry

GLA is categorized as an n−6 (also called ω−6 or omega-6) fatty acid, meaning that the first double bond on the methyl end (designated with n or ω) is the sixth bond. In physiological literature, GLA is designated as 18:3 (n−6). GLA is a carboxylic acid with an 18-carbon chain and three cis double bonds. It is a regioisomer of α-linolenic acid, which is a polyunsaturated n−3 (omega-3) fatty acid, found in rapeseed canola oil, soybeans, walnuts, flax seed (linseed oil), perilla, chia, and hemp seed.

History

GLA was first isolated from the seed oil of evening primrose. This herbal plant was grown by Native Americans to treat swelling in the body. In the 17th century, it was introduced to Europe and became a popular folk remedy, earning the name king's cure-all. In 1919, Heiduschka and Lüft extracted the oil from evening primrose seeds and described an unusual linolenic acid, which they name γ-. Later, the exact chemical structure was characterized by Riley.^[1]

Although there are α- and γ- forms of linolenic acid, there is no β- form. One was once identified, but it turned out to be an artifact of the original analytical process.^[2]

Dietary sources

GLA is obtained from vegetable oils such as evening primrose (Oenothera biennis) oil (EPO), blackcurrant seed oil, borage seed oil, and hemp seed oil. GLA is also found in varying amounts in edible hemp seeds, oats, barley,^[3] and spirulina.^[4] Normal safflower (Carthamus tinctorius) oil does not contain GLA, but a genetically modified GLA safflower oil available in commercial quantities since 2011 contains 40% GLA.^[5] Borage oil contains 20% GLA, evening primrose oil ranges from 8% to 10% GLA, and black-currant oil contains 15–20%.^[6]

The human body produces GLA from linoleic acid (LA). This reaction is catalyzed by Δ⁶-desaturase (D6D), an enzyme that allows the creation of a double bond on the sixth carbon counting from the carboxyl terminus. LA is consumed sufficiently in most diets, from such abundant sources as cooking oils and meats. However, a lack of GLA can occur when there is a reduction of the efficiency of the D6D conversion (for instance, as people grow older or when there are specific dietary deficiencies) or in disease states wherein there is excessive consumption of GLA metabolites.^[7]

Source of eicosanoids

The seed oil of Oenothera biennis (evening primrose) is a source of GLA.

From GLA, the body forms dihomo-γ-linolenic acid (DGLA). This is one of the body's three sources of eicosanoids (along with AA and EPA.) DGLA is the precursor of the prostaglandin PGH₁, which in turn forms PGE₁ and the thromboxane TXA₁. Both PGE1₁ and TXA₁ are anti-inflammatory; thromboxane TXA₁, unlike its series-2 variant, induces vasodilation, and inhibits platelet^[8] consequently, TXA₁ modulates (reduces) the pro-inflammatory properties of the thromboxane TXA₂. PGE₁ has a role in regulation of immune system function and is used as the medicine alprostadil.

Unlike AA and EPA, DGLA cannot yield leukotrienes. However, it can inhibit the formation of pro-inflammatory leukotrienes from AA.^[9]

Although GLA is an n−6 fatty acid, a type of acid that is, in general, pro-inflammatory^{[citation needed]}, it has anti-inflammatory properties. (See discussion at Essential fatty acid interactions: The paradox of dietary GLA.)

Topical use

In 2002, the UK Medicines and Healthcare products Regulatory Agency withdrew marketing authorisations for evening primrose oil as an eczema remedy.^[10]

Notes and references

^ Yung-Sheng Huang, Vincent A. Ziboh (2001). Gamma-Linolenic Acid: Recent Advances in Biotechnology and Clinical Applications. AOCS Press. p. 259. ISBN 1-893997-17-0. Retrieved 2007-12-07.
^ Eckey, EW (1954). Vegetable Fats and Oils (volume 123 of American Chemical Society monograph series). Reinhold. p. 542.
^ Qureshi A.A.; Schnoes H.K.; Din Z.Z.; Peterson D.M.; et al. (1984). "Determination of the structure of cholesterol inhibitor II isolated from high-protein barley flour (HPBF)". Fed. Proc. 43 (7): 2626.
^ Golmakani M.T.; Mendiola J.A.; Rezaei K.; Ibáñez E. (2012). "Expanded ethanol with CO
₂ and pressurized ethyl lactate to obtain fractions enriched in γ-Linolenic Acid from Arthrospira platensis (Spirulina)". J. Supercritical Fluids. 62: 109–115. doi:10.1016/j.supflu.2011.11.026. hdl:10261/43494.
^ Nykiforuk, Cory L.; et al. (19 August 2011). "High level accumulation of gamma linolenic acid (C18:3Δ6,9,12 cis) in transgenic safflower (Carthamus tinctorius) seeds". Transgenic Research. 21 (2): 367–381. doi:10.1007/s11248-011-9543-5. PMID 21853296. S2CID 17870059.
^ Flider, Frank J. (May 2005). "GLA: Uses and new sources" (PDF). INFORM. 16 (5): 279–282. Archived from the original (PDF) on 2014-01-12.
^ Horrobin D.F. (From the Efamol Research Institute. Kentville. Nova Scotia. Canada) (1993). "Fatty acid metabolism in health and disease: the role of delta-6-desaturase". American Journal of Clinical Nutrition. 57 (5 Suppl): 732S–736S, discussion 736S–737S. doi:10.1093/ajcn/57.5.732S. PMID 8386433.
^ King, Michael W. "Introduction to the Eicosanoids". The Medical Biochemistry Page. 1996–2013 themedicalbiochemistrypage.org, LLC. Retrieved 23 July 2013.
^ Belch JJ, Hill A (2000). "Evening primrose oil and borage oil in rheumatologic conditions". American Journal of Clinical Nutrition. 71 (1 Suppl): 352S–356S. doi:10.1093/ajcn/71.1.352s. PMID 10617996. DGLA itself cannot be converted to LTs but can form a 15-hydroxyl derivative that blocks the transformation of arachidonic acid to LTs. Increasing DGLA intake may allow DGLA to act as a competitive inhibitor of 2-series PGs and 4-series LTs and, thus, suppress inflammation.
^ Williams, H.C. (2003). "Evening primrose oil for atopic dermatitis: Time To Say Goodnight". BMJ. 327 (7428): 1358–9. doi:10.1136/bmj.327.7428.1358. JSTOR 25457999. PMC 292973. PMID 14670851.

[Huang-1] Yung-Sheng Huang, Vincent A. Ziboh (2001). Gamma-Linolenic Acid: Recent Advances in Biotechnology and Clinical Applications. AOCS Press. p. 259. ISBN 1-893997-17-0. Retrieved 2007-12-07.

[Eckey1954-2] Eckey, EW (1954). Vegetable Fats and Oils (volume 123 of American Chemical Society monograph series). Reinhold. p. 542.

[3] Qureshi A.A.; Schnoes H.K.; Din Z.Z.; Peterson D.M.; et al. (1984). "Determination of the structure of cholesterol inhibitor II isolated from high-protein barley flour (HPBF)". Fed. Proc. 43 (7): 2626.

[4] Golmakani M.T.; Mendiola J.A.; Rezaei K.; Ibáñez E. (2012). "Expanded ethanol with CO
₂ and pressurized ethyl lactate to obtain fractions enriched in γ-Linolenic Acid from Arthrospira platensis (Spirulina)". J. Supercritical Fluids. 62: 109–115. doi:10.1016/j.supflu.2011.11.026. hdl:10261/43494.

[5] Nykiforuk, Cory L.; et al. (19 August 2011). "High level accumulation of gamma linolenic acid (C18:3Δ6,9,12 cis) in transgenic safflower (Carthamus tinctorius) seeds". Transgenic Research. 21 (2): 367–381. doi:10.1007/s11248-011-9543-5. PMID 21853296. S2CID 17870059.

[6] Flider, Frank J. (May 2005). "GLA: Uses and new sources" (PDF). INFORM. 16 (5): 279–282. Archived from the original (PDF) on 2014-01-12.

[pmid8386433-7] Horrobin D.F. (From the Efamol Research Institute. Kentville. Nova Scotia. Canada) (1993). "Fatty acid metabolism in health and disease: the role of delta-6-desaturase". American Journal of Clinical Nutrition. 57 (5 Suppl): 732S–736S, discussion 736S–737S. doi:10.1093/ajcn/57.5.732S. PMID 8386433.

[8] King, Michael W. "Introduction to the Eicosanoids". The Medical Biochemistry Page. 1996–2013 themedicalbiochemistrypage.org, LLC. Retrieved 23 July 2013.

[Belch-9] Belch JJ, Hill A (2000). "Evening primrose oil and borage oil in rheumatologic conditions". American Journal of Clinical Nutrition. 71 (1 Suppl): 352S–356S. doi:10.1093/ajcn/71.1.352s. PMID 10617996. DGLA itself cannot be converted to LTs but can form a 15-hydroxyl derivative that blocks the transformation of arachidonic acid to LTs. Increasing DGLA intake may allow DGLA to act as a competitive inhibitor of 2-series PGs and 4-series LTs and, thus, suppress inflammation.

[goodnight-10] Williams, H.C. (2003). "Evening primrose oil for atopic dermatitis: Time To Say Goodnight". BMJ. 327 (7428): 1358–9. doi:10.1136/bmj.327.7428.1358. JSTOR 25457999. PMC 292973. PMID 14670851.

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