Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omegaâÂÂ6 fatty acid 20:4(ÃÂâÂÂ6), or 20:4(5,8,11,14). It is a precursor in the formation of leukotrienes, prostaglandins, and thromboxanes.
Together with omegaâÂÂ3 fatty acids and other omegaâÂÂ6 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.
It was named after the similarly structured Arachidic acid, a constituent of peanut oil whose name in turn derives from the ancient Greek neologism arachis 'peanut'. Peanut oil does not contain any arachidonic acid, itself. Arachidonate is the name of the derived carboxylate anion (conjugate base of the acid), salts, and some esters.
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, and liver. Skeletal muscle is an especially active site of arachidonic acid retention, accounting for roughly 10âÂÂ20% of the phospholipid fatty acid content typically.
In addition to being involved in cellular signaling as a lipid second messenger involved in the regulation of signaling enzymes, such as PLC-ó, PLC-ô, and PKC-ñ, -ò, and -ó isoforms, arachidonic acid is a key inflammatory intermediate and can also act as a vasodilator. (Note separate synthetic pathways, as described in section below.)
Arachidonic acid is synthesized from linoleic acid via a process starting with the conversion of LA into gamma-linolenic acid (GLA), effected by ÃÂ6 desaturase.
Arachidonic acid is freed from phospholipids that contain an arachidonic acid sidechain by hydrolysis, catalyzed by the phospholipase A<sub>2</sub> (PLA<sub>2</sub>).
Arachidonic acid for signaling purposes appears to be derived by the action of group IVA cytosolic phospholipase A<sub>2</sub> (cPLA<sub>2</sub>, 85 kDa), whereas inflammatory arachidonic acid is generated by the action of a low-molecular-weight secretory PLA<sub>2</sub> (sPLA<sub>2</sub>, 14-18 kDa).
Arachidonic acid is a precursor to a wide range of eicosanoids:
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.
PLA<sub>2</sub>, in turn, is activated by ligand binding to receptors, including:
Furthermore, any agent increasing intracellular calcium may cause activation of some forms of PLA<sub>2</sub>.
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.
Receptors that activate this pathway include:
PLC may also be activated by MAP kinase. Activators of this pathway include PDGF and FGF.
Along with other omegaâÂÂ6 and omegaâÂÂ3 fatty acids, arachidonic acid contributes to the structure of cell membranes. When incorporated into phospholipids, the omega fatty acid affects cell membrane properties, such as permeability and the activity of enzymes and cell-signaling mechanisms.
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. Arachidonic acid is involved in the early neurological development of infants.
Arachidonic acid is marketed as a dietary supplement. 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. 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.
A 2009 review indicated that consumption of 5âÂÂ10% of food energy from omegaâÂÂ6 fatty acids including arachidonic acid may reduce the risk of cardiovascular diseases compared to lower intakes. 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.
Cats have low ÃÂ6 desaturase activity and cannot efficiently convert linoleic acid into arachidonic acid. As a result, they need to acquire it from food.