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]
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.
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.)
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 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]
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.
PLC may also be activated by MAP kinase. Activators of this pathway include PDGF and FGF.[20]
In the body
Cell membranes
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
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
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
Aspirin—inhibits cyclooxygenase enzyme, preventing conversion of arachidonic acid to other signal molecules
^Smith WL, Song I (2002). "The enzymology of prostaglandin endoperoxide H synthases-1 and -2". Prostaglandins & Other Lipid Mediators. 68–69: 115–28. doi:10.1016/s0090-6980(02)00025-4. PMID12432913.
^Romano M, Cianci E, Simiele F, Recchiuti A (Aug 2015). "Lipoxins and aspirin-triggered lipoxins in resolution of inflammation". Eur J Pharmacol. 760: 49–63. doi:10.1016/j.ejphar.2015.03.083. PMID25895638.
^Porro B, Songia P, Squellerio I, Tremoli E, Cavalca V (Aug 2014). "Analysis, physiological and clinical significance of 12-HETE: A neglected platelet-derived 12-lipoxygenase product". J Chromatogr B. 964: 26–40. doi:10.1016/j.jchromb.2014.03.015. PMID24685839.
^Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 108. ISBN1-4160-2328-3.
^ abcdefWalter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 103. ISBN1-4160-2328-3.
^ abcdefWalter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 104. ISBN1-4160-2328-3.
^Crawford MA, Sinclair AJ (1971). "Nutritional influences in the evolution of mammalian brain. In: lipids, malnutrition & the developing brain". Ciba Foundation Symposium: 267–92. doi:10.1002/9780470719862.ch16. PMID4949878.