Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega−6 fatty acid 20:4(ω−6), or 20:4(5,8,11,14). It is a precursor in the formation of

leukotriene Leukotrienes are a family of eicosanoid inflammation, inflammatory mediators produced in leukocytes by the redox, oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxyg ...

s, prostaglandins, and thromboxanes. Together with omega−3 fatty acids and other omega−6 fatty acids, arachidonic acid provides energy for body functions, contributes to

cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

structure, and participates in the synthesis of

eicosanoid Eicosanoids are lipid signaling, signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, around 20 carbon units in length. Eicosa ...

s, which have numerous roles in physiology as signaling molecules. Its name derives from the

ancient Greek Ancient Greek (, ; ) includes the forms of the Greek language used in ancient Greece and the classical antiquity, ancient world from around 1500 BC to 300 BC. It is often roughly divided into the following periods: Mycenaean Greek (), Greek ...

neologism In linguistics, a neologism (; also known as a coinage) is any newly formed word, term, or phrase that has achieved popular or institutional recognition and is becoming accepted into mainstream language. Most definitively, a word can be considered ...

''arachis'' 'peanut', although peanut oil does not contain any arachidonic acid. Arachidonate is the name of the derived carboxylate anion ( conjugate base of the acid), salts, and some

esters In chemistry, an ester is a chemical compound, compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds c ...

Chemistry

chemical structure A chemical structure of a molecule is a spatial arrangement of its atoms and their chemical bonds. Its determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target m ...

, arachidonic acid is a

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...

with a 20-carbon chain and four '' cis''-

double bond In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betw ...

s; 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

phospholipid Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

s (especially phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositides) of membranes of the body's cells, and is abundant in the

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

muscles Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...

, and

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

. 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

Arachidonic acid is freed from

by hydrolysis, catalyzed by the phospholipase A₂ (PLA₂). 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). Arachidonic acid is a precursor to a wide range of

s: * The enzymes

cyclooxygenase Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, ) that is responsible for biosynthesis of prostanoids, including thromboxane and prostaglandins such a ...

-1 and -2 (i.e. prostaglandin G/H synthase 1 and 2 #8288;PTGS1 and PTGS2">PTGS1.html" ;"title="#8288;PTGS1">#8288;PTGS1 and PTGS2]) convert arachidonic acid to prostaglandin G2, prostaglandin G₂ and prostaglandin H2, 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). * The enzyme

5-lipoxygenase Arachidonate 5-lipoxygenase, also known as ALOX5, 5-lipoxygenase, 5-LOX, or 5-LO, is a non-heme iron-containing enzyme (EC 1.13.11.34) that in humans is encoded by the ''ALOX5'' gene. Arachidonate 5-lipoxygenase is a member of the lipoxygenase fa ...

catalyzes the oxidation of arachidonic acid to 5-hydroperoxyeicosatetraenoic acid ( 5-HPETE), which in turn converts to various

s (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 ALOX15 (also termed arachidonate 15-lipoxygenase, 15-lipoxygenase-1, 15-LO-1, 15-LOX-1) is, like other lipoxygenases, a seminal enzyme in the metabolism of polyunsaturated fatty acids to a wide range of physiologically and pathologically import ...

) and 15-lipoxygenase-2 (

ALOX15B Arachidonate 15-lipoxygenase type II is an enzyme that in humans is encoded by the ''ALOX15B'' gene. ALOX15B, also known as 15-lipoxygenase-2 (15-LO-2 or 15-LOX-2), is distinguished from its related oxygenase, ALOX15 or 15-lipoxygenase-1. Funct ...

). 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 * bFGF receptor * IFN-α receptor * IFN-γ receptor Furthermore, any agent increasing intracellular

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

may cause activation of some forms of PLA₂.

PLC activation

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: * A₁ receptor * 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. When incorporated into

s, the omega fatty acids affect cell membrane properties, such as permeability and the activity of enzymes and cell-signaling mechanisms.

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. Arachidonic acid is involved in the early neurological development of infants.

Dietary supplement

Arachidonic acid is marketed as a

dietary supplement A dietary supplement is a manufactured product intended to supplement a person's diet by taking a pill (pharmacy), pill, capsule (pharmacy), capsule, tablet (pharmacy), tablet, powder, or liquid. A supplement can provide nutrients eithe ...

. 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 effect An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term compli ...

s in adults of using high daily doses (1500 mg) of arachidonic acid on several

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...

s of blood chemistry, immune function, and

inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

. A 2009 review indicated that consumption of 5−10% of

food energy Food energy is chemical energy that animals and humans derive from food to sustain their metabolism and muscular activity. Most animals derive most of their energy from aerobic respiration, namely combining the carbohydrates, fats, and protein ...

from omega−6 fatty acids including arachidonic acid may reduce the risk of

cardiovascular disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...

s 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.

References

External links

* {{DEFAULTSORT:Arachidonic Acid Fatty acids Alkenoic acids Arachidonyl compounds