Chemistry:Docosahexaenoic acid

From HandWiki
Docosahexaenoic acid
DHA numbers.svg
Docosahexaenoic-acid-3D-balls.png
Docosahexaenoic-acid-3D-sf.png
Names
Preferred IUPAC name
(4Z,7Z,10Z,13Z,16Z,19Z)-Docosa-4,7,10,13,16,19-hexaenoic acid
Other names
cervonic acid
DHA
doconexent (INN)
Identifiers
3D model (JSmol)
Abbreviations DHA
1715505
ChEBI
ChEMBL
ChemSpider
DrugBank
EC Number
  • 612-950-9
KEGG
UNII
Properties
C22H32O2
Molar mass 328.488 g/mol
Density 0.943 g/cm3
Melting point −44 °C (−47 °F; 229 K)
Boiling point 446.7 °C (836.1 °F; 719.8 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☑Y verify (what is ☑Y☒N ?)
Infobox references
Tracking categories (test):

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, and retina. In physiological literature, it is given the name 22:6(n-3). It can be synthesized from alpha-linolenic acid or obtained directly from maternal milk (breast milk), fatty fish, fish oil, or algae oil.[1]

DHA's structure is a carboxylic acid (-oic acid) with a 22-carbon chain (docosa- derives from the Ancient Greek for 22) and six (hexa-) cis double bonds (-en-);[2] with the first double bond located at the third carbon from the omega end.[3] Its trivial name is cervonic acid (from the Latin word cerebrum for "brain"), its systematic name is all-cis-docosa-4,7,10,13,16,19-hexa-enoic acid, and its shorthand name is 22:6(n−3) in the nomenclature of fatty acids.

Most of the docosahexaenoic acid in fish and multi-cellular organisms with access to cold-water oceanic foods originates from photosynthetic and heterotrophic microalgae, and becomes increasingly concentrated in organisms the further they are up the food chain. DHA is also commercially manufactured from microalgae: Crypthecodinium cohnii and another of the genus Schizochytrium.[non-primary source needed]

In organisms that do not eat algae containing DHA nor animal products containing DHA, DHA is instead produced internally from α-linolenic acid, a shorter omega-3 fatty acid manufactured by plants (and also occurring in animal products as obtained from plants).[4] Limited amounts of eicosapentaenoic and docosapentaenoic acids are possible products of α-linolenic acid metabolism in young women[5] and men.[4] DHA in breast milk is important for the developing infant.[6] Rates of DHA production in women are 15% higher than in men.[7]

DHA is a major fatty acid in brain phospholipids and the retina. Research into the potential role or benefit of DHA in various pathologies is ongoing,[8] with significant focus on its mechanism in Alzheimer's disease[9] and cardiovascular disease.[10]

Central nervous system constituent

DHA is the most abundant omega-3 fatty acid in the brain and retina.[11] DHA comprises 40% of the polyunsaturated fatty acids (PUFAs) in the brain and 60% of the PUFAs in the retina. Fifty percent of a neuronal plasma membrane is composed of DHA.[12] DHA modulates the carrier-mediated transport of choline, glycine, and taurine, the function of delayed rectifier potassium channels, and the response of rhodopsin contained in the synaptic vesicles.[13][14]

Phosphatidylserine (PS) – which contains high DHA content – has roles in neuronal signaling and neurotransmitter synthesis,[11] and DHA deficiency is associated with cognitive decline.[11][15] DHA levels are reduced in the brain tissue of severely depressed people.[16][17]

Biosynthesis

Aerobic eukaryote pathway

Aerobic eukaryotes, specifically microalgae, mosses, fungi, and some animals, perform biosynthesis of DHA usually occurs as a series of desaturation and elongation reactions, catalyzed by the sequential action of desaturase and elongase enzymes. This pathway, originally identified in Thraustochytrium, applies to these groups:[18]

  1. a desaturation at the sixth carbon of alpha-linolenic acid by a Δ6 desaturase to produce stearidonic acid (SDA, 18:3 ω-3),
  2. elongation of the stearidonic acid by a Δ6 elongase to produce to eicosatetraenoic acid (ETA, 20:4 ω-3),
  3. desaturation at the fifth carbon of eicosatetraenoic acid by a Δ5 desaturase to produce eicosapentaenoic acid (EPA, 20:5 ω-3),
  4. elongation of eicosapentaenoic acid by a Δ5 elongase to produce docosapentaenoic acid (DPA, 22:5 ω-3), and
  5. desaturation at the fourth carbon of docosapentaenoic acid by a Δ4 desaturase to produce DHA.

Mammals

In humans, DHA is either obtained from the diet or may be converted in small amounts from eicosapentaenoic acid (EPA, 20:5, ω-3). With the identification of FADS2 as a human Δ4-desaturase in 2015, it is now known that humans also use follow latter part of the above "aerobic eukaryote" pathway, involving to Δ5-elongation to DPA and Δ4-desaturation to DHA.[19]

Although the DPA route was the original proposed pathway for humans,[5][4] scientists have long tried and failed to find a Δ4-desaturase in mammals since its proposal.[18] This gave credence to the alternative "Sprecher's shunt" hypothesis, in which EPA is twice elongated to 24:5 ω-3, then desaturated to 24:6 ω-3 (via delta 6 desaturase) in the mitochondria, then shortened to DHA (22:6 ω-3) via beta oxidation in the peroxisome.[20][21] However, the shunt model does not match clinical data, specifically as patients with beta oxidation defects do not display issues in DHA synthesis. With the identification of a Δ4-desaturase, it is considered outdated.[19]

Anaerobic pathway

Marine bacteria and the microalgae Schizochytrium use an anerobic polyketide synthase pathway to synthesize DHA.[18]

Metabolism

DHA can be metabolized into DHA-derived specialized pro-resolving mediators (SPMs), DHA epoxides, electrophilic oxo-derivatives (EFOX) of DHA, neuroprostanes, ethanolamines, acylglycerols, docosahexaenoyl amides of amino acids or neurotransmitters, and branched DHA esters of hydroxy fatty acids, among others.[22]

The enzyme CYP2C9 metabolizes DHA to epoxydocosapentaenoic acids (EDPs; primarily 19,20-epoxy-eicosapentaenoic acid isomers [i.e. 10,11-EDPs]).[23]

Potential health effects

Cardiovascular

Though mixed and plagued by methodological inconsistencies, there is now convincing evidence from ecological, RCTs, meta-analyses and animal trials show a benefit for omega-3 dietary intake for cardiovascular health.[10] Of the n-3 FAs, DHA has been argued to be the most beneficial due to its preferential uptake in the myocardium, its strongly anti-inflammatory activity and its metabolism toward neuroprotectins and resolvins, the latter of which directly contribute to cardiac function.[24]

Pregnancy and lactation

Foods high in omega-3 fatty acids may be recommended to women who want to become pregnant or when nursing.[25] A working group from the International Society for the Study of Fatty Acids and Lipids recommended 300 mg/day of DHA for pregnant and lactating women, whereas the average consumption was between 45 mg and 115 mg per day of the women in the study, similar to a Canadian study.[26]

Brain and visual functions

A major structural component of the mammalian central nervous system, DHA is the most abundant omega−3 fatty acid in the brain and retina.[27] Brain and retinal function rely on dietary intake of DHA to support a broad range of cell membrane and cell signaling properties, particularly in grey matter and retinal photoreceptor cell outer segments, which are rich in membranes.[28][29]

A systematic review found that DHA had no significant benefits in improving visual field in individuals with retinitis pigmentosa.[30] Animal research shows effect of oral intake of deuterium-reinforced DHA (D-DHA) for prevention of macular degeneration.[31]

Nutrition

Algae-based DHA supplements

Ordinary types of cooked salmon contain 500–1500 mg DHA and 300–1000 mg EPA per 100 grams.[32] Additional rich seafood sources of DHA include caviar (3400 mg per 100 grams), anchovies (1292 mg per 100 grams), mackerel (1195 mg per 100 grams), and cooked herring (1105 mg per 100 grams).[32]

Brains from mammals taken as food are also a good direct source. Beef brain, for example, contains approximately 855 mg of DHA per 100 grams in a serving.[33] While DHA may be the primary fatty acid found in certain specialized tissues, these tissues, aside from the brain, are typically small in size, such as the seminiferous tubules and the retina. As a result, animal-based foods, excluding the brain, generally offer minimal amounts of preformed DHA.[34]

Discovery of algae-based DHA

In the early 1980s, NASA sponsored scientific research on a plant-based food source that could generate oxygen and nutrition on long-duration space flights. Certain species of marine algae produced rich nutrients, leading to the development of an algae-based, vegetable-like oil that contains two polyunsaturated fatty acids, DHA and arachidonic acid.[35]

Use as a food additive

DHA is widely used as a food supplement. It was first used primarily in infant formulas.[36] In 2019, the US Food and Drug Administration published qualified health claims for DHA.[37]

Some manufactured DHA is a vegetarian product extracted from algae, and it competes on the market with fish oil that contains DHA and other omega-3s such as EPA. Both fish oil and DHA are odorless and tasteless after processing as a food additive.[38]

Studies of vegetarians and vegans

Vegetarian diets typically contain limited amounts of DHA, and vegan diets typically contain no DHA.[39] In preliminary research, algae-based supplements increased DHA levels.[40] While there is little evidence of adverse health or cognitive effects due to DHA deficiency in adult vegetarians or vegans, breast milk levels remain a concern for supplying adequate DHA to the infant.[39]

DHA and EPA in fish oils

Fish oil is widely sold in capsules containing a mixture of omega-3 fatty acids, including EPA and DHA. Oxidized fish oil in supplement capsules may contain lower levels of EPA and DHA.[41][42] Light, oxygen exposure, and heat can all contribute to oxidation of fish oil supplements.[41][42] Buying a quality product that is kept cold in storage and then keeping it in a refrigerator can help minimize oxidation.[43]

Hypothesized role in human evolution

DHA supply is a limiting factor in adult brain size.[34] An abundance of DHA in seafood has been suggested as being helpful in the development of a large brain,[44] though other researchers claim a terrestrial diet could also have provided the necessary DHA.[45]

See also

References

  1. ↑ "Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) - Implications for dietary recommendations". Biochimie 93 (1): 7–12. 2011. doi:10.1016/j.biochi.2010.05.005. PMID 20478353. 
  2. ↑ "Dictionary - Definition of DocosahexaenoicAcids". http://www.websters-online-dictionary.org/definitions/Docosahexaenoic%20Acids. 
  3. ↑ The omega end is the one furthest from the carboxyl group.
  4. ↑ 4.0 4.1 4.2 Burdge, G. C.; Jones, A. E.; Wootton, S. A. (2002). "Eicosapentaenoic and docosapentaenoic acids are the principal products of α-linolenic acid metabolism in young men". British Journal of Nutrition 88 (4): 355–363. doi:10.1079/BJN2002662. PMID 12323085. 
  5. ↑ 5.0 5.1 Burdge, G. C.; Wootton, S. A. (2002). "Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women". British Journal of Nutrition 88 (4): 411–20. doi:10.1079/BJN2002689. PMID 12323090. 
  6. ↑ Malone, J. Patrick (2012). "The Systems Theory of Autistogenesis: Putting the Pieces Together". SAGE Open 2 (2): 215824401244428. doi:10.1177/2158244012444281. 
  7. ↑ "Docosahexaenoic acid concentrations are higher in women than in men because of estrogenic effects". The American Journal of Clinical Nutrition 80 (5): 1167–74. 2004. doi:10.1093/ajcn/80.5.1167. PMID 15531662. 
  8. ↑ Ghasemi Fard, Samenah (2019). "How does high DHA fish oil affect health? A systematic review of evidence". Critical Reviews in Food Science and Nutrition 59 (11): 1684–1727. doi:10.1080/10408398.2018.1425978. PMID 29494205. 
  9. ↑ "ω-3 fatty acids in the prevention of cognitive decline in humans". Adv Nutr 4 (6): 672–6. 2013. doi:10.3945/an.113.004556. PMID 24228198. 
  10. ↑ 10.0 10.1 Innes, Jacqueline; Calder, Philip (2020). "Marine Omega-3 (N-3) Fatty Acids for Cardiovascular Health: An Update for 2020". International Journal of Molecular Sciences v (21): 1362. doi:10.3390/ijms21041362. PMID 32085487. 
  11. ↑ 11.0 11.1 11.2 Kim, Hee-Yong; Huang, Bill X.; Spector, Arthur A. (2014). "Phosphatidylserine in the brain: Metabolism and function". Progress in Lipid Research 56: 1–18. doi:10.1016/j.plipres.2014.06.002. ISSN 0163-7827. PMID 24992464. 
  12. ↑ Singh, Meharban (March 2005). "Essential fatty acids, DHA and the human brain". Indian Journal of Pediatrics 72 (3): 239–242. doi:10.1007/BF02859265. PMID 15812120. http://medind.nic.in/icb/t05/i3/icbt05i3p239.pdf. Retrieved October 8, 2007. 
  13. ↑ Spector, Arthur A.; Kim, Hee-Yong (2015). "Discovery of essential fatty acids". Journal of Lipid Research 56 (1): 11–21. doi:10.1194/jlr.r055095. ISSN 0022-2275. PMID 25339684. 
  14. ↑ Spector, Arthur A. (1999). "Essentiality of fatty acids". Lipids 34: S1–S3. doi:10.1007/BF02562220. PMID 10419080. 
  15. ↑ "A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease". J Clin Invest 115 (10): 2774–83. October 2005. doi:10.1172/JCI25420. PMID 16151530. 
  16. ↑ McNamara RK; Hahn CG; Jandacek R et al. (2007). "Selective deficits in the omega-3 fatty acid docosahexaenoic acid in the postmortem orbitofrontal cortex of patients with major depressive disorder". Biol. Psychiatry 62 (1): 17–24. doi:10.1016/j.biopsych.2006.08.026. PMID 17188654. 
  17. ↑ McNamara, R. K.; Jandacek, R; Tso, P; Dwivedi, Y; Ren, X; Pandey, G. N. (2013). "Lower docosahexaenoic acid concentrations in the postmortem prefrontal cortex of adult depressed suicide victims compared with controls without cardiovascular disease". Journal of Psychiatric Research 47 (9): 1187–91. doi:10.1016/j.jpsychires.2013.05.007. PMID 23759469. 
  18. ↑ 18.0 18.1 18.2 Qiu, Xiao (2003-02-01). "Biosynthesis of docosahexaenoic acid (DHA, 22:6-4, 7,10,13,16,19): two distinct pathways". Prostaglandins, Leukotrienes and Essential Fatty Acids 68 (2): 181–186. doi:10.1016/S0952-3278(02)00268-5. ISSN 0952-3278. PMID 12538082. 
  19. ↑ 19.0 19.1 Park, HG; Park, WJ; Kothapalli, KS; Brenna, JT (September 2015). "The fatty acid desaturase 2 (FADS2) gene product catalyzes Δ4 desaturation to yield n-3 docosahexaenoic acid and n-6 docosapentaenoic acid in human cells.". FASEB journal : official publication of the Federation of American Societies for Experimental Biology 29 (9): 3911-9. doi:10.1096/fj.15-271783. PMID 26065859. 
  20. ↑ De Caterina, R; Basta, G (June 2001). "n-3 Fatty acids and the inflammatory response – biological background". European Heart Journal Supplements 3 (Supplement D): D42–D49. doi:10.1016/S1520-765X(01)90118-X. 
  21. ↑ A Voss; M Reinhart; S Sankarappa; H Sprecher (October 1991). "The metabolism of 7,10,13,16,19-docosapentaenoic acid to 4,7,10,13,16,19-docosahexaenoic acid in rat liver is independent of a 4-desaturase". The Journal of Biological Chemistry 266 (30): 19995–20000. doi:10.1016/S0021-9258(18)54882-1. PMID 1834642. http://www.jbc.org/content/266/30/19995.full.pdf+html. Retrieved January 2, 2011. 
  22. ↑ Kuda, Ondrej (2017). "Bioactive metabolites of docosahexaenoic acid". Biochimie 136: 12–20. doi:10.1016/j.biochi.2017.01.002. PMID 28087294. 
  23. ↑ "CYP-eicosanoids--a new link between omega-3 fatty acids and cardiac disease?". Prostaglandins & Other Lipid Mediators 96 (1–4): 99–108. Nov 2011. doi:10.1016/j.prostaglandins.2011.09.001. PMID 21945326. 
  24. ↑ Mclennan, Peter (2014). "Cardiac physiology and clinical efficacy of dietary fish oil clarified through cellular mechanisms of omega-3 polyunsaturated fatty acids.". European Journal of Applied Physiology 114 (7): 1333–1356. doi:10.1007/s00421-014-2876-z. PMID 24699892. https://ro.uow.edu.au/cgi/viewcontent.cgi?article=2605&context=smhpapers. 
  25. ↑ Harvard School Of Public Health (18 September 2012). "Omega-3 Fatty Acids: An Essential Contribution". http://www.hsph.harvard.edu/nutritionsource/omega-3-fats/. 
  26. ↑ "Directly quantitated dietary (n-3) fatty acid intakes of pregnant Canadian women are lower than current dietary recommendations". The Journal of Nutrition 135 (2): 206–11. 2005. doi:10.1093/jn/135.2.206. PMID 15671214. http://jn.nutrition.org/cgi/pmidlookup?view=long&pmid=15671214. 
  27. ↑ "Nutrition for the brain: commentary on the article by Isaacs et al. on page 308". Pediatric Research 63 (3): 229–31. March 2008. doi:10.1203/pdr.0b013e318168c6d1. PMID 18287959. http://surfer.nmr.mgh.harvard.edu/ftp/articles/caudatecomm.pdf. 
  28. ↑ "Beyond building better brains: bridging the docosahexaenoic acid (DHA) gap of prematurity". Journal of Perinatology 35 (1): 1–7. January 2015. doi:10.1038/jp.2014.195. PMID 25357095. 
  29. ↑ "The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina". Progress in Retinal and Eye Research 24 (1): 87–138. January 2005. doi:10.1016/j.preteyeres.2004.06.002. PMID 15555528. 
  30. ↑ Schwartz, Stephen G.; Wang, Xue; Chavis, Pamela; Kuriyan, Ajay E.; Abariga, Samuel A. (18 June 2020). "Vitamin A and fish oils for preventing the progression of retinitis pigmentosa". The Cochrane Database of Systematic Reviews 2020 (6): CD008428. doi:10.1002/14651858.CD008428.pub3. ISSN 1469-493X. PMID 32573764. 
  31. ↑ Dunaief, Joshua L. (2022). "Heavy lipids protect against heavy metals". Aging 14 (12): 4933–4934. doi:10.18632/aging.204143. PMID 35748784. 
  32. ↑ 32.0 32.1 "EPA and DHA Content of Fish Species. Appendix G2". US Department of Agriculture. 2005. http://www.health.gov/dietaryguidelines/dga2005/report/html/table_g2_adda2.htm. 
  33. ↑ "Beef, variety meats and by-products, brain, cooked, simmered". http://nutritiondata.self.com/facts/beef-products/3463/2. 
  34. ↑ 34.0 34.1 Brenna, J. Thomas; Carlson, Susan E. (2014). "Docosahexaenoic acid and human brain development: Evidence that a dietary supply is needed for optimal development". Journal of Human Evolution 77: 99–106. doi:10.1016/j.jhevol.2014.02.017. PMID 24780861. https://doi.org/10.1016/j.jhevol.2014.02.017. 
  35. ↑ Jones, John. "Nutritional Products from Space Research". May 1st, 2001. NASA. http://www.sti.nasa.gov/tto/spinoff1996/42.html. 
  36. ↑ "FDA: Why is there interest in adding DHA and ARA to infant formulas?". US Food & Drug Administration. https://www.fda.gov/Food/FoodSafety/Product-SpecificInformation/InfantFormula/ConsumerInformationAboutInfantFormula/ucm108558.htm. 
  37. ↑ "FDA Announces New Qualified Health Claims for EPA and DHA Omega-3 Consumption and the Risk of Hypertension and Coronary Heart Disease". US Food and Drug Administration. 19 June 2019. https://www.fda.gov/food/cfsan-constituent-updates/fda-announces-new-qualified-health-claims-epa-and-dha-omega-3-consumption-and-risk-hypertension-and. 
  38. ↑ Rivlin, Gary (2007-01-14). "Magical or Overrated? A Food Additive in a Swirl". The New York Times. https://www.nytimes.com/2007/01/14/business/yourmoney/14omega.html?_r=1. 
  39. ↑ 39.0 39.1 Sanders, T. A. (2009). "DHA status of vegetarians". Prostaglandins, Leukotrienes and Essential Fatty Acids 81 (2–3): 137–41. doi:10.1016/j.plefa.2009.05.013. PMID 19500961. 
  40. ↑ Lane, K; Derbyshire, E; Li, W; Brennan, C (2014). "Bioavailability and potential uses of vegetarian sources of omega-3 fatty acids: A review of the literature". Critical Reviews in Food Science and Nutrition 54 (5): 572–9. doi:10.1080/10408398.2011.596292. PMID 24261532. 
  41. ↑ 41.0 41.1 Albert, Benjamin B (21 January 2015). "Fish oil supplements in New Zealand are highly oxidised and do not meet label content of n-3 PUFA release". Scientific Reports 5: 7928. doi:10.1038/srep07928. PMID 25604397. 
  42. ↑ 42.0 42.1 Albert, Benjamin B; Cameron-Smith, David; Hofman, Paul L.; Cutfield, Wayne S. (2013). "Oxidation of Marine Omega-3 Supplements and Human Health". BioMed Research International 2013: 464921. doi:10.1155/2013/464921. PMID 23738326. 
  43. ↑ Zargar, Atanaz; Ito, Matthew K. (1 August 2011). "Long chain omega-3 dietary supplements: a review of the National Library of Medicine Herbal Supplement Database". Metabolic Syndrome and Related Disorders 9 (4): 255–271. doi:10.1089/met.2011.0004. ISSN 1557-8518. PMID 21787228. 
  44. ↑ Crawford, M et al. (2000). "Evidence for the unique function of docosahexaenoic acid (DHA) during the evolution of the modern hominid brain". Lipids 34 (S1): S39–S47. doi:10.1007/BF02562227. PMID 10419087. 
  45. ↑ "Docosahexaenoic acid biosynthesis and dietary contingency: Encephalization without aquatic constraint". Am. J. Hum. Biol. 19 (4): 585–8. 2007. doi:10.1002/ajhb.20683. PMID 17546613. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Docosahexaenoic_acid&oldid=3339389"