Arachidonic acid
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| Names | |||
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| 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 | |||
| Identifiers | |||
3D model (JSmol)
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| 1713889 | |||
| ChEBI | |||
| ChEMBL | |||
| ChemSpider | |||
| DrugBank | |||
| ECHA InfoCard | Lua error in Module:Wikidata at line 880: attempt to index field 'wikibase' (a nil value). Lua error in Module:Wikidata at line 880: attempt to index field 'wikibase' (a nil value).Lua error in Module:EditAtWikidata at line 29: attempt to index field 'wikibase' (a nil value). | ||
| EC Number |
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| E number | Lua error in Module:Wikidata at line 880: attempt to index field 'wikibase' (a nil value). | ||
| 58972 | |||
| KEGG | |||
| MeSH | Arachidonic+acid | ||
PubChem CID
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| RTECS number |
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| UNII | |||
CompTox Dashboard (EPA)
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| 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: | |||
| GHS07: Exclamation mark | |||
| 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
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Eicosatetraenoic acid | ||
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega−6 fatty acid 20:4(ω−6), or 20:4(5,8,11,14).[2][3] It is a precursor in the formation of leukotrienes, prostaglandins, and thromboxanes.[4]
Together with omega−3 fatty acids and other omega−6 fatty acids, arachidonic acid provides energy for body functions, contributes to cell membrane structure, and participates in the synthesis of eicosanoids, which have numerous roles in physiology as signaling molecules.[2][5]
Its name derives from the ancient Greek neologism arachis 'peanut', although peanut oil does not contain any arachidonic acid.[6] Arachidonate is the name of the derived carboxylate anion (conjugate base of the acid), salts, and some esters.
Chemistry
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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
[edit | edit source]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, and liver. Skeletal muscle is an especially active site of arachidonic acid retention, accounting for roughly 10–20% of the phospholipid fatty acid content typically.[7]
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.[8] (Note separate synthetic pathways, as described in section below.)
Biosynthesis and cascade in humans
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Arachidonic acid is freed from phospholipids by hydrolysis, catalyzed by the phospholipase A2 (PLA2).[8]
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).[8]
Arachidonic acid is a precursor to a wide range of eicosanoids:
- The enzymes cyclooxygenase-1 and -2 (i.e. prostaglandin G/H synthase 1 and 2 [PTGS1 and PTGS2]) convert arachidonic acid to prostaglandin G2 and prostaglandin H2, which in turn may be converted to various prostaglandins, to prostacyclin, to thromboxanes, and to the 17-carbon product of thromboxane metabolism of prostaglandin G2/H2, 12-hydroxyheptadecatrienoic acid (12-HHT).[9][10]
- The enzyme 5-lipoxygenase catalyzes the oxidation of arachidonic acid to 5-hydroperoxyeicosatetraenoic acid (5-HPETE), which in turn converts to various leukotrienes (i.e., leukotriene B4, leukotriene C4, leukotriene D4, and leukotriene E4) as well as to 5-hydroxyeicosatetraenoic acid (5-HETE) which may then be further metabolized to 5-HETE's more potent 5-keto analog, 5-oxo-eicosatetraenoic acid (5-oxo-ETE) (also see 5-hydroxyeicosatetraenoic acid).[11]
- The enzymes 15-lipoxygenase-1 (ALOX15) and 15-lipoxygenase-2 (ALOX15B). ALOX15B catalyzes the oxidation of arachidonic acid to 15-hydroperoxyeicosatetraenoic acid (15-HPETE), which may then be further converted to 15-hydroxyeicosatetraenoic acid (15-HETE) and lipoxins;[12][13][14] 15-Lipoxygenase-1 may also further metabolize 15-HPETE to eoxins in a pathway analogous to (and presumably using the same enzymes as used in) the pathway which metabolizes 5-HPETE to leukotrienes.[15]
- The enzyme 12-lipoxygenase (ALOX12) catalyzes oxidation of arachidonic acid to 12-hydroperoxyeicosatetraenoic acid (12-HPETE), which may then be metabolized to 12-hydroxyeicosatetraenoic acid (12-HETE) and to hepoxilins.[16]
- Arachidonic acid is also a precursor to anandamide.[17]
- Some arachidonic acid is converted into hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs) by epoxygenase.[18]
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
[edit | edit source]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.[20]
PLC activation
[edit | edit source]Alternatively, arachidonic acid may be cleaved from phospholipids after phospholipase C (PLC) cleaves off the inositol trisphosphate group, yielding diacylglycerol (DAG), which subsequently is cleaved by DAG lipase to yield arachidonic acid.[19]
Receptors that activate this pathway include:
PLC may also be activated by MAP kinase. Activators of this pathway include PDGF and FGF.[20]
In the body
[edit | edit source]Cell membranes
[edit | edit source]Along with other omega−6 and omega−3 fatty acids, arachidonic acid contributes to the structure of cell membranes.[2] When incorporated into phospholipids, the omega fatty acids affect cell membrane properties, such as permeability and the activity of enzymes and cell-signaling mechanisms.[2]
Brain
[edit | edit source]Arachidonic acid, one of the most abundant fatty acids in the brain, is present in similar quantities to docosahexaenoic acid, with the two accounting for about 20% of brain fatty-acid content.[21] Arachidonic acid is involved in the early neurological development of infants.[22]
Dietary supplement
[edit | edit source]This section is missing information about Typical dietary intake — needed to put supplement dose into context. (February 2025) |
Arachidonic acid is marketed as a dietary supplement.[2][5] A 2019 review of clinical studies investigating the potential health effects of arachidonic acid supplementation of up to 1500 mg per day on human health found there were no clear benefits.[23] There were no adverse effects in adults of using high daily doses (1500 mg) of arachidonic acid on several biomarkers of blood chemistry, immune function, and inflammation.[23]
A 2009 review indicated that consumption of 5−10% of food energy from omega−6 fatty acids including arachidonic acid may reduce the risk of cardiovascular diseases compared to lower intakes.[24] A 2014 meta-analysis of possible associations between heart disease risk and individual fatty acids reported a significantly reduced risk of heart disease with higher levels of EPA, DHA, and arachidonic acid.[25]
See also
[edit | edit source]- Aspirin—inhibits cyclooxygenase enzyme, preventing conversion of arachidonic acid to other signal molecules
- Docosadienoic acid
- Fish oil
- Juniperonic acid, an isomer
- Polyunsaturated fat
References
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External links
[edit | edit source]- Arachidonic+Acid at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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