Arachidonic acid

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 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. 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. (Note separate synthetic pathways, as described in section below.) ==Biosynthesis and cascade in humans==

De novo Arachidonic acid is synthesized from linoleic acid (LA) via a process starting with the conversion of LA into gamma-linolenic acid (GLA), effected by Δ6 desaturase. By hydrolysis Arachidonic acid is freed from phospholipids that contain an arachidonic acid sidechain by hydrolysis, catalyzed by the phospholipase A2 (PLA2). • 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). • 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; 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. • 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. • Arachidonic acid is also a precursor to anandamide. • Some arachidonic acid is converted into hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs) by epoxygenase. 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 • mGLUR1 • D2 receptor • α2 adrenergic receptor • 5-HT1 receptor PLC may also be activated by MAP kinase. Activators of this pathway include PDGF and FGF. ==In the body==

Cell membranes Along with other omega−6 and omega−3 fatty acids, arachidonic acid contributes to the structure of cell membranes. Arachidonic acid is involved in the early neurological development of infants. ==Dietary supplement==

Arachidonic acid is marketed as a dietary supplement. 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 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. == Veterinary medicine ==

Cats have low Δ6 desaturase activity and cannot efficiently convert linoleic acid into arachidonic acid. As a result, they need to acquire it from food. ==See also==