Arachidonic acid
| |||
Names | |||
---|---|---|---|
Preferred IUPAC name
(5Z,8Z,11Z,14Z)-Icosa-5,8,11,14-tetraenoic acid[1] | |||
Other names
5,8,11,14-all-cis-Eicosatetraenoic acid; all-cis-5,8,11,14-Eicosatetraenoic acid; Arachidonate
| |||
Identifiers | |||
3D model (
JSmol ) |
|||
3DMet | |||
1713889 | |||
ChEBI | |||
ChEMBL | |||
ChemSpider | |||
DrugBank | |||
ECHA InfoCard
|
100.007.304 | ||
EC Number |
| ||
58972 | |||
IUPHAR/BPS |
|||
KEGG | |||
MeSH | Arachidonic+acid | ||
PubChem CID
|
|||
RTECS number
|
| ||
UNII | |||
CompTox Dashboard (EPA)
|
|||
| |||
| |||
Properties | |||
C20H32O2 | |||
Molar mass | 304.474 g·mol−1 | ||
Density | 0.922 g/cm3 | ||
Melting point | −49 °C (−56 °F; 224 K) | ||
Boiling point | 169 to 171 °C (336 to 340 °F; 442 to 444 K) at 0.15 mmHg | ||
log P | 6.994 | ||
Acidity (pKa) | 4.752 | ||
Hazards | |||
GHS labelling: | |||
Warning | |||
H302, H312, H315, H319, H332, H335 | |||
P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P312, P304+P340, P305+P351+P338, P312, P321, P322, P330, P332+P313, P337+P313, P362, P363, P403+P233, P405, P501 | |||
NFPA 704 (fire diamond) | |||
Flash point | 113 °C (235 °F; 386 K) | ||
Related compounds | |||
Related compounds
|
Eicosatetraenoic acid | ||
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
|
Arachidonic acid (AA, sometimes ARA) is a
Chemistry
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.
Biology
Arachidonic acid is a polyunsaturated fatty acid present in the
In addition to being involved in
Conditionally essential fatty acid
Arachidonic acid is not one of the essential fatty acids. However, it does become essential if a deficiency in linoleic acid exists or if an inability to convert linoleic acid to arachidonic acid occurs.
Some mammals lack the ability or have a very limited capacity to convert linoleic acid to arachidonic acid, making it an essential part of their diets. (As linoleic acid consumption does not seem to affect levels of arachidonic acid in plasma/serum or erythrocytes, it is uncertain if humans can in fact convert linoleic acid to arachidonic acid.
Biosynthesis and cascade in humans
Arachidonic acid is freed from phospholipid by hydrolysis, catalyzed by the phospholipase A2 (PLA2).[6]
Arachidonic acid for signaling purposes appears to be derived by the action of group IVA 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).[6]
Arachidonic acid is a precursor to a wide range of eicosanoids:
- The enzymes
- The enzyme 5-oxo-eicosatetraenoic acid (5-oxo-ETE) (also see 5-Hydroxyeicosatetraenoic acid).[13]
- The enzymes 15-lipoxygenase-1 (
- The enzyme 12-lipoxygenase (12-hydroxyeicosatetraenoic acid (12-HETE) and to hepoxilins.[18]
- Arachidonic acid is also a precursor to anandamide.[19]
- Some arachidonic acid is converted into
The production of these derivatives and their actions in the body are collectively known as the "arachidonic acid cascade"; see Essential fatty acid interactions and the enzyme and metabolite linkages given in the previous paragraph for more details.
PLA2 activation
PLA2, in turn, is activated by ligand binding to receptors, including:
- 5-HT2 receptors [21]
- mGLUR1[21]
- bFGF receptor[21]
- IFN-α receptor[21]
- IFN-γ receptor[21]
Furthermore, any agent increasing intracellular calcium may cause activation of some forms of PLA2.[22]
PLC activation
Alternatively, arachidonic acid may be cleaved from phospholipids after
Receptors that activate this pathway include:
PLC may also be activated by
In the body
Muscle growth
Arachidonic acid promotes the repair and growth of skeletal muscle tissue via conversion to prostaglandin
Brain
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 about 20% of its fatty-acid content.[24] Like DHA, neurological health is reliant upon sufficient levels of arachidonic acid. Among other things, arachidonic acid helps to maintain hippocampal cell membrane fluidity.[25] It also helps protect the brain from oxidative stress by activating peroxisome proliferator-activated receptor gamma.[26] AA also activates syntaxin-3 (STX-3), a protein involved in the growth and repair of neurons.[27]
Arachidonic acid is also involved in early neurological development. In one study, infants (18 months) given supplemental arachidonic acid for 17 weeks demonstrated significant improvements in intelligence, as measured by the Mental Development Index.[28] This effect is further enhanced by the simultaneous supplementation of AA with DHA.
In adults, the disturbed metabolism of AA may contribute to neuropsychiatric disorders such as Alzheimer's disease and bipolar disorder.[29] There is evidence of significant alterations in the conversion of arachidonic acid to other bioactive molecules (overexpression or disturbances in the AA enzyme cascade) in these conditions.
Alzheimer's disease
The biological roles of arachidonic acid and its metabolites have been explored in the context of various
Bodybuilding supplement
Arachidonic acid is marketed as an
Dietary arachidonic acid and inflammation
Increased consumption of arachidonic acid will not cause inflammation during normal metabolic conditions unless
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 with 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.[medical citation needed] 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 AA supplementation does not appear to have proinflammatory effects in healthy individuals, it may counter the anti-inflammatory effects of omega-3 fatty acid supplementation.[37]
Health effects of arachidonic acid supplementation
Arachidonic acid supplementation in daily doses 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,[34] serum lipids,[38] immunity,[39] and platelet aggregation[33] appear to be unaffected with this level and duration of use. Furthermore, higher concentrations of AA in muscle tissue may be correlated with improved insulin sensitivity.[40] Arachidonic acid supplementation of the diets of healthy adults appears to offer no toxicity or significant safety risk.
While studies looking at arachidonic acid supplementation in sedentary subjects have failed to find changes in resting inflammatory markers in doses up to 1,500 mg daily, strength-trained subjects may respond differently. One study reported a significant reduction in resting inflammation (via marker IL-6) in young men supplementing 1,000 mg/day of arachidonic acid for 50 days in combination with resistance training. This suggests that rather than being pro-inflammatory, supplementation of AA while undergoing resistance training may actually improve the regulation of systemic inflammation.[41]
A meta-analysis looking for associations between heart disease risk and individual fatty acids reported a significantly reduced risk of heart disease with higher levels of EPA and DHA (omega-3 fats), as well as the omega-6 arachidonic acid.[42] A scientific advisory from the American Heart Association has also favorably evaluated the health impact of dietary omega-6 fats, including arachidonic acid.[32] 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. It suggests dietary AA is not a risk factor for heart disease, and may play a role in maintaining optimal metabolism and reduced heart disease risk. Maintaining sufficient intake levels of both omega-3 and omega-6 fatty acids, therefore, is recommended for optimal health.
Arachidonic acid is not carcinogenic, and studies show dietary level is not associated (positively or negatively) with risk of cancers.[43][44][45][46] AA 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 with cancer, inflammatory, or other diseased states is unknown, and supplementation is not recommended.
See also
- Aspirin—inhibits cyclooxygenase enzyme, preventing conversion of arachidonic acid to other signal molecules
- Fish oil
- Polyunsaturated fat
References
- ^ Pubchem. "5,8,11,14-Eicosatetraenoic acid | C20H32O2 - PubChem". pubchem.ncbi.nlm.nih.gov. Retrieved 2016-03-31.
- ^ "IUPAC Lipid nomenclature: Appendix A: names of and symbols for higher fatty acids". www.sbcs.qmul.ac.uk.
- ^ "Dorland's Medical Dictionary – 'A'". Archived from the original on 11 January 2007. Retrieved 2007-01-12.
- S2CID 1522233.
- PMID 21501117.
- ^ ISBN 0-7234-3341-0.
- PMID 21663641.
- PMID 6380542.
- S2CID 4287904.
- ^ Production of life'sARA™ Archived 2016-07-01 at the Wayback Machine, www.lifesdha.com/
- PMID 4723909.
- PMID 12432913.
- PMID 25449650.
- PMID 9177185.
- S2CID 2723454.
- PMID 25895638.
- PMID 18184802.
- PMID 24685839.
- S2CID 205133026.
- ISBN 1-4160-2328-3.
- ^ ISBN 1-4160-2328-3.
- ^ ISBN 1-4160-2328-3.
- ^ PMID 23539318.
- PMID 4949878.
- S2CID 11284462.
- PMID 16982041.
- S2CID 4411524.
- S2CID 30740256.
- PMID 19022981.
- S2CID 234486305.
- PMID 33803760.
- ^ S2CID 15072227.
- ^ S2CID 4053608.
- ^ a b Changes in whole blood and clinical safety markers over 50 days of concomitant arachidonic acid supplementation and resistance training Archived 2011-07-07 at the Wayback Machine. 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.
- PMID 12877651.
- PMID 16234304.
- PMID 7852864.
- S2CID 4056220.
- S2CID 3970315.
- PMID 8418404.
- PMID 18045476.
- PMID 24723079.
- PMID 10491529.
- PMID 15213050.
- PMID 16123006.
- PMID 15570048.
External links
- Arachidonic Acid at acnp.org
- Arachidonic+Acid at the U.S. National Library of Medicine Medical Subject Headings (MeSH)