Eicosapentaenoic acid

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Eicosapentaenoic acid
Eicosapentaenoic acid
Eicosapentaenoic acid spacefill.png
Names
Preferred IUPAC name
(5Z,8Z,11Z,14Z,17Z)-Icosa-5,8,11,14,17-pentaenoic acid
Other names
(5Z,8Z,11Z,14Z,17Z)-5,8,11,14,17-eicosapentaenoic acid
Identifiers
3D model (JSmol)
3DMet
1714433
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.117.069 Edit this at Wikidata
KEGG
UNII
  • InChI=1S/C20H30O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20(21)22/h3-4,6-7,9-10,12-13,15-16H,2,5,8,11,14,17-19H2,1H3,(H,21,22)/b4-3-,7-6-,10-9-,13-12-,16-15- checkY
    Key: JAZBEHYOTPTENJ-JLNKQSITSA-N checkY
  • InChI=1/C20H30O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20(21)22/h3-4,6-7,9-10,12-13,15-16H,2,5,8,11,14,17-19H2,1H3,(H,21,22)/b4-3-,7-6-,10-9-,13-12-,16-15-
    Key: JAZBEHYOTPTENJ-JLNKQSITBZ
  • O=C(O)CCC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CC
Properties
C20H30O2
Molar mass 302.451 g/mol
Hazards
GHS pictograms GHS05: Corrosive
GHS Signal word Danger
H314
P260, P264, P280, P301+330+331, P303+361+353, P304+340, P305+351+338, P310, P321, P363, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)
Infobox references

Eicosapentaenoic acid (EPA; also icosapentaenoic acid) is an omega-3 fatty acid. In physiological literature, it is given the name 20:5(n-3). It also has the trivial name timnodonic acid. In chemical structure, EPA is a carboxylic acid with a 20-carbon chain and five cis double bonds; the first double bond is located at the third carbon from the omega end.

EPA is a polyunsaturated fatty acid (PUFA) that acts as a precursor for prostaglandin-3 (which inhibits platelet aggregation), thromboxane-3, and leukotriene-5 eicosanoids. EPA is both a precursor and the hydrolytic breakdown product of eicosapentaenoyl ethanolamide (EPEA: C22H35NO2; 20:5,n-3).[1] Although studies of fish oil supplements, which contain both docosahexaenoic acid (DHA) and EPA, have failed to support claims of preventing heart attacks or strokes,[2][3][4] a recent multi-year study of Vascepa (ethyl eicosapentaenoate, the ethyl ester of the free fatty acid), a prescription drug containing only EPA, was shown to reduce heart attack, stroke, and cardiovascular death by 25% relative to a placebo in those with statin-resistant hypertriglyceridemia.[5][6]

Sources[edit]

EPA is obtained in the human diet by eating oily fish or fish oil, e.g. cod liver, herring, mackerel, salmon, menhaden and sardine, and various types of edible algae. It is also found in human breast milk.

However, fish can either synthesize EPA from fatty acids precursors found in their alimentation[7] or obtain it from the algae they consume.[8] It is available to humans from some non-animal sources (e.g. commercially, from Yarrowia lipolytica,[9] and from microalgae such as Monodus subterraneus, Chlorella minutissima and Phaeodactylum tricornutum,[10][11] which are being developed as a commercial source).[12] EPA is not usually found in higher plants, but it has been reported in trace amounts in purslane.[13] In 2013, it was reported that a genetically modified form of the plant camelina produced significant amounts of EPA.[14][15]

The human body converts a portion of absorbed alpha-linolenic acid (ALA) to EPA. ALA is itself an essential fatty acid, an appropriate supply of which must be ensured. The efficiency of the conversion of ALA to EPA, however, is much lower than the absorption of EPA from food containing it. Because EPA is also a precursor to docosahexaenoic acid (DHA), ensuring a sufficient level of EPA on a diet containing neither EPA nor DHA is harder both because of the extra metabolic work required to synthesize EPA and because of the use of EPA to metabolize into DHA. Medical conditions like diabetes or certain allergies may significantly limit the human body's capacity for metabolization of EPA from ALA.

Biosynthesis of Eicosapentaenoic Acid[edit]

The biosynthesis of Eicosapentaenoic acid (EPA) in prokaryotes and eukaryotes involves polyketide synthase (PKS). The polyketide pathway includes six enzymes namely, 3-ketoacyl synthase (KS), 2 ketoacyl-ACP-reductase(KR), dehydrase (DH), enoyl reductase (ER), dehydratase/2-trans 3-cos isomerase (DH/2,3I), dehydratase/2-trans, and 2-cis isomerase(DH/2,2I). The biosynthesis of EPA varies in marine species but most of the marine species ability to convert C18 PUFA to LC-PUFA is dependent on the fatty acyl desaturase and elongase enzymes. The molecule basis of the enzymes will dictate where the double bond is formed on the resulting molecule product.[16]

Here is an overview of the possible biosynthesis pathways of EPA from fatty acid synthesis (FAS). The reactions are mediated by desaturases enzymes with Δx specificity and elongated by elongases of fatty acid chains.

Overview of biosynthesis of EPA from FAS


The propose polyketide synthesis pathway of EPA in Shewanella is a repetitive reaction of reduction, dehydration, and condensation that uses acetyl coA and malonyl coA as building blocks. The mechanism of α-linolenic acid to EPA involves the condensation of malonyl-CoA to the pre-existing α-linolenic acid by KS. The resulting structure is converted by NADPH dependent reductase, KR, to form an intermediate that is dehydrated by the DH enzyme. The final step is the NADPH-dependent reduction of a double bond in trans-2-enoly-ACP via ER enzyme activity. The process is repeated to form EPA.[17]

α-linolenic acid to EPA

Clinical significance[edit]

Salmon is a rich source of EPA.

The US National Institute of Health's MedlinePlus lists medical conditions for which EPA (alone or in concert with other ω-3 sources) is known or thought to be an effective treatment.[18] Most of these involve its ability to lower inflammation.

Intake of large doses (2.0 to 4.0 g/day) of long-chain omega-3 fatty acids as prescription drugs or dietary supplements are generally required to achieve significant (> 15%) lowering of triglycerides, and at those doses the effects can be significant (from 20% to 35% and even up to 45% in individuals with levels greater that 500 mg/dL).

It appears that both EPA and DHA lower triglycerides; however, DHA appears to raise low-density lipoprotein (the variant which drives atherosclerosis, sometimes inaccurately called "bad cholesterol") and LDL-C values (always only a calculated estimate; not measured by labs from person's blood sample for technical and cost reasons), while EPA does not.

EPA and DHA ethyl esters (all forms) may be absorbed less well, thus work less well, when taken on an empty stomach or with a low-fat meal.[19]

Omega-3 fatty acids, particularly EPA, have been studied for their effect on autistic spectrum disorder (ASD). Some have theorized that, since omega-3 fatty acid levels may be low in children with autism, supplementation might lead to an improvement in symptoms. While some uncontrolled studies have reported improvements, well-controlled studies have shown no statistically significant improvement in symptoms as a result of high-dose omega-3 supplementation.[20][21]

In addition, studies have shown that omega-3 fatty acids may be useful for treating depression.[20][22]

References[edit]

  1. ^ Lucanic M, Held JM, Vantipalli MC, Klang IM, Graham JB, Gibson BW, Lithgow GJ, Gill MS (May 2011). "N-acylethanolamine signalling mediates the effect of diet on lifespan in Caenorhabditis elegans". Nature. 473 (7346): 226–9. Bibcode:2011Natur.473..226L. doi:10.1038/nature10007. PMC 3093655. PMID 21562563.
  2. ^ Zimmer C (September 17, 2015). "Inuit Study Adds Twist to Omega-3 Fatty Acids' Health Story". The New York Times. Retrieved October 11, 2015.
  3. ^ O'Connor A (March 30, 2015). "Fish Oil Claims Not Supported by Research". The New York Times. Retrieved October 11, 2015.
  4. ^ Grey A, Bolland M (March 2014). "Clinical trial evidence and use of fish oil supplements". JAMA Internal Medicine. 174 (3): 460–2. doi:10.1001/jamainternmed.2013.12765. PMID 24352849.
  5. ^ Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM (January 3, 2019). "Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia". New England Journal of Medicine. 380 (1): 11–22. doi:10.1056/NEJMoa1812792. PMID 30415628.
  6. ^ "Vascepa® (icosapent ethyl) 26% Reduction in Key Secondary Composite Endpoint of Cardiovascular Death, Heart Attacks and Stroke Demonstrated in REDUCE-IT™". November 10, 2018. Retrieved January 21, 2019.
  7. ^ Committee on the Nutrient Requirements of Fish and Shrimp; National Research Council (2011). Nutrient requirements of fish and shrimp. Washington, DC: The National Academies Press. ISBN 978-0-309-16338-5.CS1 maint: multiple names: authors list (link)
  8. ^ Bishop-Weston Y. "Plant based sources of vegan & vegetarian Docosahexaenoic acid – DHA and Eicosapentaenoic acid EPA & Essential Fats". Archived from the original on 2013-05-22. Retrieved 2008-08-05.
  9. ^ Xie, Dongming; Jackson, Ethel N.; Zhu, Quinn (February 2015). "Sustainable source of omega-3 eicosapentaenoic acid from metabolically engineered Yarrowia lipolytica: from fundamental research to commercial production". Applied Microbiology and Biotechnology. 99 (4): 1599–1610. doi:10.1007/s00253-014-6318-y. ISSN 0175-7598. PMC 4322222. PMID 25567511.
  10. ^ Vazhappilly R, Chen F (1998). "Eicosapentaenoic acid and docosahexaenoic acid production potential of microalgae and their heterotrophic growth". Journal of the American Oil Chemists' Society. 75 (3): 393–397. doi:10.1007/s11746-998-0057-0. S2CID 46917269.
  11. ^ Ratha SK, Prasanna R (February 2012). "Bioprospecting microalgae as potential sources of "Green Energy"—challenges and perspectives". Applied Biochemistry and Microbiology. 48 (2): 109–125. doi:10.1134/S000368381202010X. PMID 22586907.
  12. ^ Halliday J (12 January 2007). "Water 4 to introduce algae DHA/EPA as food ingredient". Retrieved 2007-02-09.
  13. ^ Simopoulos AP (2002). "Omega-3 fatty acids in wild plants, nuts and seeds" (PDF). Asia Pacific Journal of Clinical Nutrition. 11 (Suppl 2): S163–73. doi:10.1046/j.1440-6047.11.s.6.5.x. Archived from the original (PDF) on 2008-12-17.
  14. ^ Ruiz-Lopez N, Haslam RP, Napier JA, Sayanova O (January 2014). "Successful high-level accumulation of fish oil omega-3 long-chain polyunsaturated fatty acids in a transgenic oilseed crop". The Plant Journal. 77 (2): 198–208. doi:10.1111/tpj.12378. PMC 4253037. PMID 24308505.
  15. ^ Coghlan A (4 January 2014). "Designed plant oozes vital fish oils". New Scientist. 221 (2950): 12. doi:10.1016/s0262-4079(14)60016-6.
  16. ^ Monroig, Óscar; Tocher, Douglas; Navarro, Juan (2013-10-21). "Biosynthesis of Polyunsaturated Fatty Acids in Marine Invertebrates: Recent Advances in Molecular Mechanisms". Marine Drugs. 11 (10): 3998–4018. doi:10.3390/md11103998. PMC 3826146.
  17. ^ Moi, Ibrahim Musa; Leow, Adam Thean Chor; Ali, Mohd Shukuri Mohamad; Rahman, Raja Noor Zaliha Raja Abd.; Salleh, Abu Bakar; Sabri, Suriana (July 2018). "Polyunsaturated fatty acids in marine bacteria and strategies to enhance their production". Applied Microbiology and Biotechnology. 102 (14): 5811–5826. doi:10.1007/s00253-018-9063-9.
  18. ^ NIH Medline Plus. "MedlinePlus Herbs and Supplements: Omega-3 fatty acids, fish oil, alpha-linolenic acid". Archived from the original on February 8, 2006. Retrieved February 14, 2006.
  19. ^ Jacobson TA, Maki KC, Orringer CE, Jones PH, Kris-Etherton P, Sikand G, La Forge R, Daniels SR, Wilson DP, Morris PB, Wild RA, Grundy SM, Daviglus M, Ferdinand KC, Vijayaraghavan K, Deedwania PC, Aberg JA, Liao KP, McKenney JM, Ross JL, Braun LT, Ito MK, Bays HE, Brown WV, Underberg JA (2015). "National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2". Journal of Clinical Lipidology. 9 (6 Suppl): S1–122.e1. doi:10.1016/j.jacl.2015.09.002. PMID 26699442.
  20. ^ a b Bent S, Bertoglio K, Hendren RL (August 2009). "Omega-3 fatty acids for autistic spectrum disorder: a systematic review". Journal of Autism and Developmental Disorders. 39 (8): 1145–54. doi:10.1007/s10803-009-0724-5. PMC 2710498. PMID 19333748.
  21. ^ Mankad D, Dupuis A, Smile S, Roberts W, Brian J, Lui T, Genore L, Zaghloul D, Iaboni A, Marcon PM, Anagnostou E (2015-03-21). "A randomized, placebo controlled trial of omega-3 fatty acids in the treatment of young children with autism". Molecular Autism. 6: 18. doi:10.1186/s13229-015-0010-7. PMC 4367852. PMID 25798215.
  22. ^ Ilardi, Stephen. "Therapeutic Lifestyle Change. A new treatment for depression". Therapeutic Lifestyle Change (TLC). Retrieved 9 November 2019. We were never designed for the sedentary, indoor, sleep-deprived, socially-isolated, fast-food-laden, frenetic pace of modern life.

External links[edit]