| Arachidonic acid |
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(5Z,8Z,11Z,14Z)-5,8,11,14-Eicosatetraenoic acid
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(5Z,8Z,11Z,14Z)-Icosa-5,8,11,14-tetraenoic acid[1]
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Other names
5,8,11,14-all-cis-Eicosatetraenoic acid; all-cis-5,8,11,14-Eicosatetraenoic acid; Arachidonate
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| Identifiers |
| CAS number |
506-32-1  Y |
| PubChem |
444899 |
| ChemSpider |
392692 Y |
| UNII |
27YG812J1I Y |
| EC number |
208-033-4 |
| DrugBank |
DB04557 |
| KEGG |
C00219  N |
| MeSH |
Arachidonic+acid |
| ChEBI |
CHEBI:36306 N |
| ChEMBL |
CHEMBL15594 Y |
| RTECS number |
CE6675000 |
| Beilstein Reference |
1713889 |
| 3DMet |
B00061 |
| Jmol-3D images |
Image 1 |
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CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCCC(=O)O
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InChI=1S/C20H32O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20(21)22/h6-7,9-10,12-13,15-16H,2-5,8,11,14,17-19H2,1H3,(H,21,22) N
Key: YZXBAPSDXZZRGB-UHFFFAOYSA-N N
InChI=1S/C20H32O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20(21)22/h6-7,9-10,12-13,15-16H,2-5,8,11,14,17-19H2,1H3,(H,21,22)/b7-6-,10-9-,13-12-,16-15-
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| Properties |
| Molecular formula |
C20H32O2 |
| Molar mass |
304.47 g mol−1 |
| Density |
0.922 g/cm3 |
| Melting point |
-49 °C, 224 K, -56 °F
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| Boiling point |
169-171 °C, 442-444 K, 336-340 °F (at 0.15 mmHg)
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| log P |
6.994 |
| Acidity (pKa) |
4.752 |
| Hazards |
| R-phrases |
R19 |
| NFPA 704 |
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| Flash point |
113 °C (235 °F) |
 N (verify) (what is:  Y/ N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) |
| Infobox references |
Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6). It is the counterpart to the saturated arachidic acid found in peanut oil, (L. arachis – peanut.)[2]
In chemical structure, arachidonic acid is a carboxylic acid with a 20-carbon chain and four cis-double bonds; the first double bond is located at the sixth carbon from the omega end.
Some chemistry sources define 'arachidonic acid' to designate any of the eicosatetraenoic acids. However, almost all writings in biology, medicine and nutrition limit the term to all-cis-5,8,11,14-eicosatetraenoic acid.
Arachidonic acid is a polyunsaturated fatty acid present in the phospholipids (especially phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositides) of membranes of the body's cells, and is abundant in the brain, muscles, liver.
In addition to being involved in cellular signaling as a lipid second messenger involved in the regulation of signaling enzymes, such as PLC-γ, PLC-δ, and PKC-α, -β, and -γ isoforms, arachidonic acid is a key inflammatory intermediate and can also act as a vasodilator.[3] (Note separate synthetic pathways, as described in section below)
Arachidonic acid in the human body usually comes from dietary animal sources—meat, eggs, dairy—or is synthesized from linoleic acid.
Arachidonic acid is not one of the essential fatty acids. However, it does become essential if there is a deficiency in linoleic acid or if there is an inability to convert linoleic acid to arachidonic acid, which is required by most mammals. Some mammals lack the ability to—or have a very limited capacity to—convert linoleic acid into arachidonic acid, making it an essential part of their diets. Since little or no arachidonic acid is found in common plants, such animals are obligate carnivores; the cat is a common example.[4][5] A commercial source of arachidonic acid has been derived, however, from the fungus Mortierella alpina.[6]
Arachidonic acid is freed from a phospholipid molecule by the enzyme phospholipase A2 (PLA2), which cleaves off the fatty acid, but can also be generated from DAG by diacylglycerol lipase.[3]
Arachidonic acid generated for signaling purposes appears to be derived by the action of a phosphatidylcholine-specific cytosolic phospholipase A2 (cPLA2, 85 kDa), whereas inflammatory arachidonic acid is generated by the action of a low-molecular-weight secretory PLA2 (sPLA2, 14-18 kDa).[3]
Arachidonic acid is a precursor in the production of eicosanoids:
The production of these derivatives and their action in the body are collectively known as the "arachidonic acid cascade"; see essential fatty acid interactions for more details.
[edit] PLA2 activation
PLA2, in turn, is activated by ligand binding to receptors, including:
Furthermore, any agent increasing intracellular calcium may cause activation of some forms of PLA2.[9]
Alternatively, arachidonic acid may be cleaved from phospholipids by phospholipase C (PLC), yielding diacylglycerol (DAG), which subsequently is cleaved by DAG lipase to yield arachidonic acid.[8]
Receptors that activate this pathway include:
PLC may also be activated by MAP kinase. Activators of this pathway include PDGF and FGF.[9]
Through its conversion to active components such as the prostaglandin PGF2alpha, arachidonic acid is necessary for the repair and growth of skeletal muscle tissue.[10] This role makes ARA an important dietary component in support of the muscle anabolic process. One of the lead researchers of the Baylor study (see Bodybuilding section) on arachidonic acid, Mike Roberts MS, CSCS, has authored an article published under the title Arachidonic Acid, The New Mass Builder explaining the role of this nutrient in muscle anabolism, and its potential for the enhancement of muscle size and strength.[11] The paper explains that for optimal muscle growth, a training stimulus must elicit localized inflammation and soreness. It explains that arachidonic acid (AA, 20:4n-6) is an essential omega-6 (1-6) polyunsaturated fatty acid that is abundant in skeletal muscle membrane phospholipids (figure 2). It is also the body's principal building block for the production of prostaglandins, which are known to have various physiological roles, including a close involvement in inflammation. Also, the prostaglandin isomer PGF2a has a potent ability to stimulate muscle growth. As such, arachidonic acid is a regulator of localized muscle inflammation, and may be a central nutrient controlling the intensity of the anabolic/tissue-rebuilding response to weight training.
Arachidonic acid is one of the most abundant fatty acids in the brain, and is present in similar quantities to docosahexaenoic acid (DHA). The two account for approximately 20% of its fatty acid content.[12] Like DHA, neurological health is reliant upon sufficient levels of arachidonic acid. Among other things, arachidonic acid helps to maintain hippocampal cell membrane fluidity.[13] It also helps protect the brain from oxidative stress by activating peroxisome proliferator-activated receptor gamma.[14] ARA also activates syntaxin-3 (STX-3), a protein involved in the growth and repair of neurons.[15]
Arachidonic acid is also involved in early neurological development. In one study funded by the U.S. National Institute of Child Health and Human Development, infants (18 months) given supplemental arachidonic acid for 17 weeks demonstrated significant improvements in intelligence, as measured by the Mental Development Index.[16] This effect is further enhanced by the simultaneous supplementation of ARA with DHA.
In adults, the disturbed metabolism of ARA may be associated with neurological disorders such as Alzheimer’s disease and Bipolar disorder.[17] This may involve significant alterations in the conversion of arachidonic acid to other bioactive molecules (overexpression or disturbances in the ARA enzyme cascade). Notably, dietary arachidonic acid consumption is not associated with the onset of Alzheimer's disease, and studies suggest the supplementation of arachidonic acid during the early stages of this disease may actually be effective in reducing symptoms and slowing the disease progress.[18] Additional studies on arachidonic acid supplementation for Alzheimer's patients are needed.
Arachidonic acid is marketed as an anabolic bodybuilding supplement in a variety of products. The first clinical study concerning the use of arachidonic acid as a sport supplement[19] found the following statistically significant improvement, and statistically strong trends:
A significant group × time interaction for relative Wingate peak power was observed among groups (P = 0.02) with gains in peak power being significantly greater in the AA group (0.3 ± 1.2 W·kg-1) vs. PLA (0.2 ± 0.7 W·kg-1, Figure 1). Using repeated measures ANOVA with delta scores, the AA group experienced significantly greater increases in comparison to the PLA group at day 50 (P < 0.05). Statistical trends were seen in Wingate total work (AA: 1,292 ± 1,206 vs. PLA: 510 ± 1,249 J, P = 0.09, ηp 2 = 0.052), favoring the AA group.
With regard to inflammation, the paper reported a statistically significant reduction in resting IL-6 levels (a central regulator of inflammation):
IL-6 levels experienced a significant group × time interaction (P = 0.04) among groups with subsequent post hoc analyses revealing that IL-6 was significantly lower at day 25 of the study. One-way ANOVA of IL-6 delta values at day 25 revealed significantly greater increases in PLA when compared to AA group (AA: 0.8 ± 13.5 pg·ml-1 vs. PLA: 52.5 ± 1.6 pg·ml-1, P = 0.01; Figure 2)
Arachidonic acid was shown to improve peak muscle power, reduce resting IL-6 levels, and produce statistically strong trends of improvements in muscle endurance, average power, and bench press 1-rep maximum lift. This study provided preliminary evidence supporting the use of arachidonic acid in sports nutrition.
Under normal metabolic conditions, the increased consumption of arachidonic acid is unlikely to increase inflammation. ARA is metabolized to both proinflammatory and anti-inflammatory molecules.[20] Studies giving between 840 mg and 2,000 mg per day to healthy individuals for up to 50 days have shown no increases in inflammation or related metabolic activities.[20][21][22][23] Increased arachidonic acid levels are actually associated with reduced pro-inflammatory IL-6 and IL-1 levels, and increased anti-inflammatory tumor necrosis factor-beta.[24] This may result in a reduction in systemic inflammation.
Arachidonic acid does still play a central role in inflammation related to injury and many diseased states. How it is metabolized in the body dictates its inflammatory or anti-inflammatory activity. Individuals suffering from joint pains or active inflammatory disease may find that increased arachidonic acid consumption exacerbates symptoms, presumably because it is being more readily converted to inflammatory compounds. Likewise, high arachidonic acid consumption is not advised for individuals with a history of inflammatory disease, or who are in compromised health. Of note, while ARA supplementation does not appear to have proinflammatory effects in healthy individuals, it may counter the anti-inflammatory effects of omega-3 fatty acid supplementation.[25]
Arachidonic acid supplementation in daily dosages of 1,000-1,500 mg for 50 days has been well tolerated during several clinical studies, with no significant side effects reported. All common markers of health, including kidney and liver function,[22] serum lipids,[26] immunity,[27] and platelet aggregation[21] appear to be unaffected with this level and duration of use. Furthermore, higher concentrations of ARA in muscle tissue may be correlated with improved insulin sensitivity.[28] Arachidonic acid supplementation of the diets of healthy adults appears to offer no toxicity or significant safety risk.
A scientific advisory from the American Heart Association has favorably evaluated the health impact of dietary omega-6 fats, including arachidonic acid.[29] The group does not recommend limiting this essential fatty acid. In fact, the paper recommends individuals follow a diet that consists of at least 5-10% of calories coming from omega-6 fats, including arachidonic acid. Dietary ARA is not a risk factor for heart disease, and may play a role in maintaining optimal metabolism and reduced heart disease risk. It is, therefore, recommended to maintain sufficient intake levels of both omega-3 and omega-6 essential fatty acids for optimal health.
Arachidonic acid is not carcinogenic, and studies show dietary level is not associated (positively or negatively) with risk of cancers.[30][31][32][33] ARA remains integral to the inflammatory and cell growth process, however, which is disturbed in many types of disease including cancer. Therefore, the safety of arachidonic acid supplementation in patients suffering from cancer, inflammatory, or other diseased states is unknown, and supplementation is not recommended.
- ^ http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=231
- ^ "Dorland's Medical Dictionary – 'A'". http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSzdmd_a_56zPzhtm. Retrieved 2007-01-12.
- ^ a b c Baynes, John W.; Marek H. Dominiczak (2005). Medical Biochemistry 2nd. Edition. Elsevier Mosby. p. 555. ISBN 0-7234-3341-0.
- ^ MacDonald, ML; Rogers, QR; Morris, JG (1984). "Nutrition of the Domestic Cat, a Mammalian Carnivore". Annual Review of Nutrition 4: 521–62. DOI:10.1146/annurev.nu.04.070184.002513. PMID 6380542.
- ^ Rivers, JP; Sinclair, AJ; Craqford, MA (1975). "Inability of the cat to desaturate essential fatty acids". Nature 258 (5531): 171–3. Bibcode 1975Natur.258..171R. DOI:10.1038/258171a0. PMID 1186900.
- ^ History of Martek, Martek.com
- ^ Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 108. ISBN 1-4160-2328-3.
- ^ a b c d e f Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 103. ISBN 1-4160-2328-3.
- ^ a b c d e f Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. pp. 104. ISBN 1-4160-2328-3.
- ^ Trappe, TA; Fluckey, JD; White, F; Lambert, CP; Evans, WJ (2001). "Skeletal muscle PGF(2)(alpha) and PGE(2) in response to eccentric resistance exercise: influence of ibuprofen acetaminophen.". The Journal of Clinical Endocrinology and Metabolism 86 (10): 5067–70. DOI:10.1210/jc.86.10.5067. PMID 11600586.
- ^ http://www.bodybuilding.com/fun/llewellyn2.htm
- ^ Crawford, MA; Sinclair, AJ (1971). "Nutritional influences in the evolution of mammalian brain. In: lipids, malnutrition & the developing brain". Ciba Foundation symposium: 267–92. PMID 4949878.
- ^ Fukaya, T.; Gondaira, T.; Kashiyae, Y.; Kotani, S.; Ishikura, Y.; Fujikawa, S.; Kiso, Y.; Sakakibara, M. (2007). "Arachidonic acid preserves hippocampal neuron membrane fluidity in senescent rats". Neurobiology of Aging 28 (8): 1179–1186. DOI:10.1016/j.neurobiolaging.2006.05.023. PMID 16790296. edit
- ^ Wang, ZJ; Liang, CL; Li, GM; Yu, CY; Yin, M (2006). "Neuroprotective effects of arachidonic acid against oxidative stress on rat hippocampal slices". Chemico-biological interactions 163 (3): 207–17. DOI:10.1016/j.cbi.2006.08.005. PMID 16982041.
- ^ Darios, F; Davletov, B (2006). "Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on syntaxin 3.". Nature 440 (7085): 813–7. Bibcode 2006Natur.440..813D. DOI:10.1038/nature04598. PMID 16598260.
- ^ Developmental Medicine and Child Neurology, March 2000[page needed]
- ^ Rapoport, SI (2008). "Arachidonic acid and the brain". The Journal of nutrition 138 (12): 2515–20. PMID 19022981.
- ^ Schaeffer, EL; Forlenza, OV; Gattaz, WF (2009). "Phospholipase A2 activation as a therapeutic approach for cognitive enhancement in early-stage Alzheimer disease". Psychopharmacology 202 (1–3): 37–51. DOI:10.1007/s00213-008-1351-0. PMID 18853146.
- ^ Roberts, MD; Iosia, M; Kerksick, CM; Taylor, LW; Campbell, B; Wilborn, CD; Harvey, T; Cooke, M et al. (2007). "Effects of arachidonic acid supplementation on training adaptations in resistance-trained males". Journal of the International Society of Sports Nutrition 4: 21. DOI:10.1186/1550-2783-4-21. PMC 2217562. PMID 18045476. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2217562.
- ^ a b Harris, WS; Mozaffarian, D; Rimm, E; Kris-Etherton, P; Rudel, LL; Appel, LJ; Engler, MM; Engler, MB et al. (2009). "Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention". Circulation 119 (6): 902–7. DOI:10.1161/CIRCULATIONAHA.108.191627. PMID 19171857.
- ^ a b Nelson, GJ; Schmidt, PC; Bartolini, G; Kelley, DS; Kyle, D (1997). "The effect of dietary arachidonic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans". Lipids 32 (4): 421–5. DOI:10.1007/s11745-997-0055-7. PMID 9113631.
- ^ a b Changes in whole blood and clinical safety markers over 50 days of concomitant arachidonic acid supplementation and resistance training. Wilborn, C, M Roberts, C Kerksick, M Iosia, L Taylor, B Campbell, T Harvey, R Wilson, M. Greenwood, D Willoughby and R Kreider. Proceedings of the International Society of Sports Nutrition (ISSN) Conference June 15–17, 2006. http://arachidonic.com/ARA-baylorsafety.pdf
- ^ Pantaleo, P; Marra, F; Vizzutti, F; Spadoni, S; Ciabattoni, G; Galli, C; La Villa, G; Gentilini, P et al. (2004). "Effects of dietary supplementation with arachidonic acid on platelet and renal function in patients with cirrhosis". Clinical science 106 (1): 27–34. DOI:10.1042/CS20030182. PMID 12877651.
- ^ Ferrucci, L; Cherubini, A; Bandinelli, S; Bartali, B; Corsi, A; Lauretani, F; Martin, A; Andres-Lacueva, C et al. (2006). "Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers". The Journal of Clinical Endocrinology and Metabolism 91 (2): 439–46. DOI:10.1210/jc.2005-1303. PMID 16234304.
- ^ Li, B; Birdwell, C; Whelan, J (1994). "Antithetic relationship of dietary arachidonic acid and eicosapentaenoic acid on eicosanoid production in vivo". Journal of lipid research 35 (10): 1869–77. PMID 7852864.
- ^ Nelson, GJ; Schmidt, PC; Bartolini, G; Kelley, DS; Phinney, SD; Kyle, D; Silbermann, S; Schaefer, EJ (1997). "The effect of dietary arachidonic acid on plasma lipoprotein distributions, apoproteins, blood lipid levels, and tissue fatty acid composition in humans". Lipids 32 (4): 427–33. DOI:10.1007/s11745-997-0056-6. PMID 9113632.
- ^ Kelley, DS; Taylor, PC; Nelson, GJ; MacKey, BE (1998). "Arachidonic acid supplementation enhances synthesis of eicosanoids without suppressing immune functions in young healthy men". Lipids 33 (2): 125–30. DOI:10.1007/s11745-998-0187-9. PMID 9507233.
- ^ Borkman, M; Storlien, LH; Pan, DA; Jenkins, AB; Chisholm, DJ; Campbell, LV (1993). "The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids". The New England Journal of Medicine 328 (4): 238–44. DOI:10.1056/NEJM199301283280404. PMID 8418404.
- ^ Harris, WS; Mozaffarian, D; Rimm, E; Kris-Etherton, P; Rudel, LL; Appel, LJ; Engler, MM; Engler, MB et al. (2009). "Omega-6 Fatty Acids and Risk for Cardiovascular Disease: A Science Advisory From the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention". Circulation 119 (6): 902–7. DOI:10.1161/CIRCULATIONAHA.108.191627. PMID 19171857.
- ^ Schuurman, AG; Van Den Brandt, PA; Dorant, E; Brants, HA; Goldbohm, RA (1999). "Association of energy and fat intake with prostate carcinoma risk: results from The Netherlands Cohort Study". Cancer 86 (6): 1019–27. DOI:10.1002/(SICI)1097-0142(19990915)86:6<1019::AID-CNCR18>3.0.CO;2-H. PMID 10491529.
- ^ Leitzmann, MF; Stampfer, MJ; Michaud, DS; Augustsson, K; Colditz, GC; Willett, WC; Giovannucci, EL (2004). "Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer". The American journal of clinical nutrition 80 (1): 204–16. PMID 15213050.
- ^ Astorg, P (2005). "Dietary fatty acids and colorectal and prostate cancers: epidemiological studies". Bulletin du cancer 92 (7): 670–84. PMID 16123006.
- ^ Whelan, J; McEntee, MF (2004). "Dietary (n-6) PUFA and intestinal tumorigenesis". The Journal of nutrition 134 (12 Suppl): 3421S–3426S. PMID 15570048.
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| Precursor |
Arachidonic acid
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| Prostanoids |
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| Leukotrienes (LT) |
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| Nonclassic |
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| By function |
bronchoconstriction (PGD2, TXA2, LTC4, LTD4, LTE4)
vasoconstriction (PGF2α, TXA2, TXB2) · vasodilation (PGE2, PGI2, LTC4, LTD4, LTE4)
platelets: induce (TXA2) inhibit (PGD2, PGI2) · leukocytes: induce (TXA2, LTB4) inhibit (PGD2, PGE2)
fever stimulation: (PGE2)
labor stimulation: ( PGE2 (Dinoprostone), PGF2α (Dinoprost))
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