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{{Short description|Fatty acid used metabolically in many organisms}}
{{Short description|Fatty acid used metabolically in many organisms}}
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| ImageFileL2 = Arachidonic acid spacefill.png
| ImageFileL2 = Arachidonic acid spacefill.png
| ImageFileR2 = Arachidonic acid2.png
| ImageFileR2 = Arachidonic acid2.png
| PIN = (5''Z'',8''Z'',11''Z'',14''Z'')-Icosa-5,8,11,14-tetraenoic acid<ref>{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=231|title=5,8,11,14-Eicosatetraenoic acid {{!}} C20H32O2 - PubChem|last=Pubchem|website=pubchem.ncbi.nlm.nih.gov|access-date=2016-03-31}}</ref>
| PIN = (5''Z'',8''Z'',11''Z'',14''Z'')-Icosa-5,8,11,14-tetraenoic acid<ref>{{Cite web |url=https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=231 |title=5,8,11,14-Eicosatetraenoic acid {{!}} C20H32O2 - PubChem |last=Pubchem |website=pubchem.ncbi.nlm.nih.gov |access-date=2016-03-31}}</ref>
| OtherNames = 5,8,11,14-''all''-''cis''-Eicosatetraenoic acid; ''all''-''cis''-5,8,11,14-Eicosatetraenoic acid; Arachidonate
| OtherNames = 5,8,11,14-''all''-''cis''-Eicosatetraenoic acid<br/>''all''-''cis''-5,8,11,14-Eicosatetraenoic acid
|Section1={{Chembox Identifiers
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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).<ref>{{cite web |title=IUPAC Lipid nomenclature: Appendix A: names of and symbols for higher fatty acids |url=http://www.sbcs.qmul.ac.uk/iupac/lipid/appABC.html#appA |website=www.sbcs.qmul.ac.uk}}</ref> It is structurally related to the saturated [[arachidic acid]] found in [[Cupuaçu|cupuaçu butter]].<ref name=Dorland>{{cite web|
'''Arachidonic acid''' ('''AA''', sometimes '''ARA''') is a [[polyunsaturated]] [[omega-6 fatty acid]] 20:4(ω-6), or 20:4(5,8,11,14).<ref name="lpi">{{cite web |title=Essential fatty acids |url=https://lpi.oregonstate.edu/mic/other-nutrients/essential-fatty-acids |publisher=Micronutrient Information Center, Linus Pauling Institute, Oregon State University |access-date=13 May 2024 |date=June 2019}}</ref><ref>{{cite web |title=IUPAC Lipid nomenclature: Appendix A: names of and symbols for higher fatty acids |url=http://www.sbcs.qmul.ac.uk/iupac/lipid/appABC.html#appA |website=www.sbcs.qmul.ac.uk}}</ref> If its precursors or diet contains [[linoleic acid]] it is formed by biosynthesis and can be deposited in animal [[fat]]s. It is a [[Precursor (chemistry)|precursor]] in the formation of [[leukotriene]]s, [[prostaglandin]]s, and [[thromboxane]]s.<ref name=Dorland>{{cite web |title=Dorland's Medical Dictionary – 'A' |url=http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSzdmd_a_56zPzhtm |access-date=2007-01-12 |archive-url=https://web.archive.org/web/20070111113516/http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSzdmd_a_56zPzhtm |archive-date=11 January 2007 |url-status=live}}</ref>

title = Dorland's Medical Dictionary – 'A'
Together with [[omega-3 fatty acid]]s and other omega-6 fatty acids, arachidonic acid provides energy for body functions, contributes to [[cell membrane]] structure, and participates in the synthesis of [[eicosanoid]]s, which have numerous roles in physiology as [[Cell signaling|signaling molecules]].<ref name=lpi/><ref name="ods">{{cite web |title=Omega-3 fatty acids |url=https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/ |publisher=Office of Dietary Supplements, US National Institutes of Health |access-date=13 May 2024 |date=15 February 2023}}</ref>
| url= http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSzdmd_a_56zPzhtm

| access-date = 2007-01-12| archive-url= https://web.archive.org/web/20070111113516/http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSzdmd_a_56zPzhtm| archive-date= 11 January 2007 | url-status= live}}</ref> Its name derives from the [[New Latin]] word ''arachis'' (peanut), but it is important to note that [[peanut oil]] does not contain any arachidonic acid.<ref>{{cite journal |title=Arachidonic acid and peanut oil|url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(94)91695-0/fulltext|journal=The Lancet|year=1994|doi=10.1016/S0140-6736(94)91695-0|last1=Truswell|first1=A.S.|last2=Choudhury|first2=N.|last3=Peterson|first3=D.B.|last4=Mann|first4=J.I.|last5=Agostoni|first5=Carlos|last6=Riva|first6=Enrica|last7=Giovannini|first7=Marcello|last8=Marangoni|first8=Franca|last9=Galli|first9=Claudio|volume=344|issue=8928|pages=1030–1031|pmid=7999151|s2cid=1522233}}</ref>
Its name derives from the [[ancient Greek]] [[neologism]] ''arachis'' 'peanut', but [[peanut oil]] does not contain any arachidonic acid.<ref>{{cite journal |title=Arachidonic acid and peanut oil |url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(94)91695-0/fulltext |journal=The Lancet |year=1994 |doi=10.1016/S0140-6736(94)91695-0 |last1=Truswell |first1=A.S. |last2=Choudhury |first2=N. |last3=Peterson |first3=D.B. |last4=Mann |first4=J.I. |last5=Agostoni |first5=Carlos |last6=Riva |first6=Enrica |last7=Giovannini |first7=Marcello |last8=Marangoni |first8=Franca |last9=Galli |first9=Claudio |volume=344 |issue=8928 |pages=1030–1031 |pmid=7999151 |s2cid=1522233|url-access=subscription }}</ref> '''Arachidonate''' is the name of the derived [[carboxylate anion]] ([[conjugate base]] of the acid), salts, and some [[carboxylate ester|esters]].

==Chemistry==
==Chemistry==
[[File:AAnumbering.png|300px]]
[[File:AAnumbering.png|300px]]
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In [[chemical structure]], arachidonic acid is a [[carboxylic acid]] with a 20-carbon chain and four ''[[Cis–trans isomerism|cis]]''-[[double bond]]s; the first double bond is located at the sixth carbon from the omega end.
In [[chemical structure]], arachidonic acid is a [[carboxylic acid]] with a 20-carbon chain and four ''[[Cis–trans isomerism|cis]]''-[[double bond]]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 acid]]s. However, almost all writings in biology, medicine, and nutrition limit the term to all ''cis''-5,8,11,14-eicosatetraenoic acid.
Some chemistry sources define 'arachidonic acid' to designate any of the [[eicosatetraenoic acid]]s. However, almost all writings in biology, medicine, and nutrition limit the term to ''all cis''-5,8,11,14-eicosatetraenoic acid.


==Biology==
==Biology==
Arachidonic acid is a polyunsaturated fatty acid present in the [[phospholipid]]s (especially [[phosphatidylethanolamine]], [[phosphatidylcholine]], and [[phosphatidylinositide]]s) of [[cell membrane|membranes]] of the body's [[cell (biology)|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.<ref>{{cite journal|last1=Smith|first1=GI|last2=Atherton|first2=P|last3=Reeds|first3=DN|last4=Mohammed|first4=BS|last5=Rankin|first5=D|last6=Rennie|first6=MJ|last7=Mittendorfer|first7=B|title=Omega-3 polyunsaturated fatty acids augment the muscle protein anabolic response to hyperinsulinaemia-hyperaminoacidaemia in healthy young and middle-aged men and women.|journal=Clinical Science|date=Sep 2011|volume=121|issue=6|pages=267–78|pmid=21501117|doi=10.1042/cs20100597|pmc=3499967}}</ref>
Arachidonic acid is a polyunsaturated fatty acid present in the [[phospholipid]]s (especially [[phosphatidylethanolamine]], [[phosphatidylcholine]], and [[phosphatidylinositide]]s) of [[cell membrane|membranes]] of the body's [[cell (biology)|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.<ref>{{cite journal |last1=Smith |first1=GI |last2=Atherton |first2=P |last3=Reeds |first3=DN |last4=Mohammed |first4=BS |last5=Rankin |first5=D |last6=Rennie |first6=MJ |last7=Mittendorfer |first7=B |title=Omega-3 polyunsaturated fatty acids augment the muscle protein anabolic response to hyperinsulinaemia-hyperaminoacidaemia in healthy young and middle-aged men and women. |journal=Clinical Science |date=Sep 2011 |volume=121 |issue=6 |pages=267–78 |pmid=21501117 |doi=10.1042/cs20100597 |pmc=3499967}}</ref>


In addition to being involved in [[cellular signaling]] as a lipid [[second messenger]] involved in the regulation of signaling enzymes, such as [[Phospholipase C|PLC]]-γ, PLC-δ, and [[Protein kinase C|PKC]]-α, -β, and -γ isoforms, arachidonic acid is a key inflammatory intermediate and can also act as a [[vasodilator]].<ref name=Dominiczak>{{cite book |last= Baynes |first= John W. |author2= Marek H. Dominiczak |title= Medical Biochemistry 2nd. Edition |publisher= [[Elsevier|Elsevier Mosby]] |year= 2005 |page= [https://archive.org/details/medicalbiochemis0000unse/page/555 555] |isbn= 0-7234-3341-0 |url-access= registration |url= https://archive.org/details/medicalbiochemis0000unse/page/555 }}</ref> (Note separate synthetic pathways, as described in section below.)
In addition to being involved in [[cellular signaling]] as a lipid [[second messenger]] involved in the regulation of signaling enzymes, such as [[Phospholipase C|PLC]]-γ, PLC-δ, and [[Protein kinase C|PKC]]-α, -β, and -γ isoforms, arachidonic acid is a key inflammatory intermediate and can also act as a [[vasodilator]].<ref name=Dominiczak>{{cite book |last=Baynes |first=John W. |author2=Marek H. Dominiczak |title=Medical Biochemistry 2nd. Edition |publisher=[[Elsevier|Elsevier Mosby]] |year=2005 |page=[https://archive.org/details/medicalbiochemis0000unse/page/555 555] |isbn=0-7234-3341-0 |url-access=registration |url=https://archive.org/details/medicalbiochemis0000unse/page/555}}</ref> (Note separate synthetic pathways, as described in section below.)

==Conditionally essential fatty acid==
{{Main|Essential fatty acid}}

[[Image:Ribeyes.jpeg|thumb|right|250px|Arachidonic acid in the human body usually comes from dietary animal sources (meat, eggs).]]

Arachidonic acid is not one of the [[essential fatty acid]]s. However, it does become essential if a deficiency in [[linoleic acid]] exists or if an inability to convert linoleic acid to arachidonic acid occurs.
Some mammals lack the ability or have a very limited capacity to convert linoleic acid to arachidonic acid, making it an essential part of their diets. Since linoleic acid consumption does not seem to affect levels of arachidonic acid in plasma/serum or erythrocytes, it is uncertain if humans can in fact convert linoleic acid to arachidonic acid.<ref>{{cite journal |last1=Rett |first1=BS |last2=Whelan |first2=Jay |title=Increasing dietary linoleic acid does not increase tissue arachidonic acid content in adults consuming Western-type diets: a systematic review |journal=Nutrition and Metabolism |date=10 June 2011 |volume=8 |issue=36 |page=1, 13 |doi=10.1186/1743-7075-8-36 |pmid=21663641 |pmc=3132704 |ref=Rett}}</ref> Since little or no arachidonic acid is found in common plants, such animals are obligate [[carnivore]]s; the cat is a common example of having the inability to desaturate essential fatty acids.<ref name=carnivore>{{cite journal |last1=MacDonald |first1=ML |last2=Rogers |first2=QR |last3=Morris |first3=JG |title=Nutrition of the Domestic Cat, a Mammalian Carnivore |journal=Annual Review of Nutrition |volume=4 |pages=521–62 |year=1984 |pmid=6380542 |doi=10.1146/annurev.nu.04.070184.002513}}</ref><ref name=Sinclair>{{cite journal |last1=Rivers |first1=JP |last2=Sinclair |first2=AJ |last3=Craqford |first3=MA |title=Inability of the cat to desaturate essential fatty acids |doi=10.1038/258171a0 |journal=Nature |pmid=1186900 |year=1975 |volume=258 |issue=5531 |pages=171–3|bibcode = 1975Natur.258..171R |s2cid=4287904 }}</ref> A commercial source of arachidonic acid has been derived, however, from the fungus ''[[Mortierella|Mortierella alpina]]''.<ref>[http://www.lifesdha.com/dha-at-every-age/infants/what-is-ara.aspx Production of life'sARA™], www.lifesdha.com/</ref>


==Biosynthesis and cascade in humans==
==Biosynthesis and cascade in humans==
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Arachidonic acid is a precursor to a wide range of [[eicosanoid]]s:
Arachidonic acid is a precursor to a wide range of [[eicosanoid]]s:
* 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 [[prostaglandin]]s, to [[prostacyclin]], to [[thromboxane]]s, and to the 17-carbon product of thromboxane metabolism of prostaglandin G2/H2, [[12-Hydroxyheptadecatrienoic acid]] (12-HHT).<ref>{{cite journal|pmid=4723909 |year=1973 |last1=Wlodawer |first1=P |title=On the organization and mechanism of prostaglandin synthetase |journal=The Journal of Biological Chemistry |volume=248 |issue=16 |pages=5673–8 |last2=Samuelsson |first2=B |doi=10.1016/S0021-9258(19)43558-8 |doi-access=free }}</ref><ref>{{cite journal|pmid=12432913|year=2002|last1=Smith|first1=W. L.|title=The enzymology of prostaglandin endoperoxide H synthases-1 and -2|journal=Prostaglandins & Other Lipid Mediators|volume=68–69|pages=115–28|last2=Song|first2=I|doi=10.1016/s0090-6980(02)00025-4}}</ref>
* 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 [[prostaglandin]]s, to [[prostacyclin]], to [[thromboxane]]s, and to the 17-carbon product of thromboxane metabolism of prostaglandin G2/H2, [[12-hydroxyheptadecatrienoic acid]] (12-HHT).<ref>{{cite journal |pmid=4723909 |year=1973 |last1=Wlodawer |first1=P |title=On the organization and mechanism of prostaglandin synthetase |journal=The Journal of Biological Chemistry |volume=248 |issue=16 |pages=5673–8 |last2=Samuelsson |first2=B |doi=10.1016/S0021-9258(19)43558-8 |doi-access=free}}</ref><ref>{{cite journal |pmid=12432913 |year=2002 |last1=Smith |first1=W. L. |title=The enzymology of prostaglandin endoperoxide H synthases-1 and -2 |journal=Prostaglandins & Other Lipid Mediators |volume=68–69 |pages=115–28 |last2=Song |first2=I |doi=10.1016/s0090-6980(02)00025-4}}</ref>
* The enzyme [[5-lipoxygenase]] catalyzes the oxidation of arachidonic acid to 5-hydroperoxyeicosatetraenoic acid ([[5-HPETE]]), which in turn converts to various [[leukotriene]]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]].<ref>{{cite journal | date = Apr 2015 | title = Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid| journal = Biochim Biophys Acta | volume = 1851 | issue = 4| pages = 340–355 | doi = 10.1016/j.bbalip.2014.10.008 | pmid=25449650| last1 = Powell| first1 = W. S.| last2 = Rokach| first2 = J| pmc = 5710736}}</ref>
* The enzyme [[5-lipoxygenase]] catalyzes the oxidation of arachidonic acid to 5-hydroperoxyeicosatetraenoic acid ([[5-HPETE]]), which in turn converts to various [[leukotriene]]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]]).<ref>{{cite journal |date=Apr 2015 |title=Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid |journal=Biochim Biophys Acta |volume=1851 |issue=4 |pages=340–355 |doi=10.1016/j.bbalip.2014.10.008 |pmid=25449650 |last1=Powell |first1=W. S. |last2=Rokach |first2=J |pmc=5710736}}</ref>
* The enzymes 15-lipoxygenase-1 ([[ALOX15]] and 15-lipoxygenase-2 ([[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]];<ref>{{cite journal | date = Jun 1997 | title = Discovery of a second 15S-lipoxygenase in humans| journal = Proc Natl Acad Sci U S A | volume = 94 | issue = 12| pages = 6148–52 | pmid = 9177185| pmc = 21017| last1 = Brash| first1 = A. R.| last2 = Boeglin| first2 = W. E.| last3 = Chang| first3 = M. S. | doi=10.1073/pnas.94.12.6148| bibcode = 1997PNAS...94.6148B| doi-access = free}}</ref><ref>{{cite journal | date = May 2012 | title = Role of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in hypoxia-induced pulmonary hypertension| journal = J Physiol Sci | volume = 62 | issue = 3| pages = 163–72 | doi = 10.1007/s12576-012-0196-9 | pmid=22331435| last1 = Zhu| first1 = D| last2 = Ran| first2 = Y| s2cid = 2723454| doi-access = free}}</ref><ref>{{cite journal | date = Aug 2015 | title = Lipoxins and aspirin-triggered lipoxins in resolution of inflammation| journal = Eur J Pharmacol | volume = 760 | pages = 49–63 | doi = 10.1016/j.ejphar.2015.03.083 | pmid=25895638| last1 = Romano| first1 = M| last2 = Cianci| first2 = E| last3 = Simiele| first3 = F| last4 = Recchiuti| first4 = A}}</ref> 15-Lipoxygenase-1 may also further metabolize 15-HPETE to [[eoxin]]s in a pathway analogous to (and presumably using the same enzymes as used in) the pathway which metabolizes 5-HPETE to leukotrienes.<ref>{{cite journal | date = Jan 2008 | title = Eoxins are proinflammatory arachidonic acid metabolites produced via the 15-lipoxygenase-1 pathway in human eosinophils and mast cells| journal = Proc Natl Acad Sci U S A | volume = 105 | issue = 2| pages = 680–5 | doi = 10.1073/pnas.0710127105 | pmid=18184802 | pmc=2206596| last1 = Feltenmark| first1 = S| last2 = Gautam| first2 = N| last3 = Brunnström| first3 = A| last4 = Griffiths| first4 = W| last5 = Backman| first5 = L| last6 = Edenius| first6 = C| last7 = Lindbom| first7 = L| last8 = Björkholm| first8 = M| last9 = Claesson| first9 = H. E.| bibcode = 2008PNAS..105..680F| doi-access = free}}</ref>
* 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]];<ref>{{cite journal |date=Jun 1997 |title=Discovery of a second 15S-lipoxygenase in humans |journal=Proc Natl Acad Sci U S A |volume=94 |issue=12 |pages=6148–52 |pmid=9177185 |pmc=21017 |last1=Brash |first1=A. R. |last2=Boeglin |first2=W. E. |last3=Chang |first3=M. S. |doi=10.1073/pnas.94.12.6148 |bibcode=1997PNAS...94.6148B |doi-access=free}}</ref><ref>{{cite journal |date=May 2012 |title=Role of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in hypoxia-induced pulmonary hypertension |journal=J Physiol Sci |volume=62 |issue=3 |pages=163–72 |doi=10.1007/s12576-012-0196-9 |pmid=22331435 |last1=Zhu |first1=D |last2=Ran |first2=Y |s2cid=2723454 |doi-access=free|pmc=10717549 }}</ref><ref>{{cite journal |date=Aug 2015 |title=Lipoxins and aspirin-triggered lipoxins in resolution of inflammation |journal=Eur J Pharmacol |volume=760 |pages=49–63 |doi=10.1016/j.ejphar.2015.03.083 |pmid=25895638 |last1=Romano |first1=M |last2=Cianci |first2=E |last3=Simiele |first3=F |last4=Recchiuti |first4=A}}</ref> 15-Lipoxygenase-1 may also further metabolize 15-HPETE to [[eoxin]]s in a pathway analogous to (and presumably using the same enzymes as used in) the pathway which metabolizes 5-HPETE to leukotrienes.<ref>{{cite journal |date=Jan 2008 |title=Eoxins are proinflammatory arachidonic acid metabolites produced via the 15-lipoxygenase-1 pathway in human eosinophils and mast cells |journal=Proc Natl Acad Sci U S A |volume=105 |issue=2 |pages=680–5 |doi=10.1073/pnas.0710127105 |pmid=18184802 |pmc=2206596 |last1=Feltenmark |first1=S |last2=Gautam |first2=N |last3=Brunnström |first3=A |last4=Griffiths |first4=W |last5=Backman |first5=L |last6=Edenius |first6=C |last7=Lindbom |first7=L |last8=Björkholm |first8=M |last9=Claesson |first9=H. E. |bibcode=2008PNAS..105..680F |doi-access=free}}</ref>
* 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]].<ref>{{cite journal | date = Aug 2014 | title = Analysis, physiological and clinical significance of 12-HETE: A neglected platelet-derived 12-lipoxygenase product| journal = J Chromatogr B | volume = 964 | pages = 26–40 | doi = 10.1016/j.jchromb.2014.03.015 | pmid=24685839| last1 = Porro| first1 = B| last2 = Songia| first2 = P| last3 = Squellerio| first3 = I| last4 = Tremoli| first4 = E| last5 = Cavalca| first5 = V}}</ref>
* 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 [[hepoxilin]]s.<ref>{{cite journal |date=Aug 2014 |title=Analysis, physiological and clinical significance of 12-HETE: A neglected platelet-derived 12-lipoxygenase product |journal=J Chromatogr B |volume=964 |pages=26–40 |doi=10.1016/j.jchromb.2014.03.015 |pmid=24685839 |last1=Porro |first1=B |last2=Songia |first2=P |last3=Squellerio |first3=I |last4=Tremoli |first4=E |last5=Cavalca |first5=V}}</ref>
* Arachidonic acid is also a precursor to [[anandamide]].<ref>{{cite journal | date = May 2013 | title = Metabolism of endocannabinoids and related N -acylethanolamines: Canonical and alternative pathways| journal = FEBS J. | volume = 280 | issue = 9| pages = 1874–94 | doi = 10.1111/febs.12152 | pmid = 23425575| last1 = Ueda| first1 = Natsuo| last2 = Tsuboi| first2 = Kazuhito| last3 = Uyama| first3 = Toru| s2cid = 205133026| doi-access = free}}</ref>
* Arachidonic acid is also a precursor to [[anandamide]].<ref>{{cite journal |date=May 2013 |title=Metabolism of endocannabinoids and related N -acylethanolamines: Canonical and alternative pathways |journal=FEBS J. |volume=280 |issue=9 |pages=1874–94 |doi=10.1111/febs.12152 |pmid=23425575 |last1=Ueda |first1=Natsuo |last2=Tsuboi |first2=Kazuhito |last3=Uyama |first3=Toru |s2cid=205133026 |doi-access=free}}</ref>
* Some arachidonic acid is converted into [[hydroxyeicosatetraenoic acid (disambiguation)|hydroxyeicosatetraenoic acids]] (HETEs) and [[epoxyeicosatrienoic acid]]s (EETs) by [[epoxygenase]].<ref name=boron108>{{cite book |author=Walter F., PhD. Boron |title=Medical Physiology: A Cellular And Molecular Approaoch |publisher=Elsevier/Saunders |year=2003 |page=108 |isbn=1-4160-2328-3}}</ref>
* Some arachidonic acid is converted into [[hydroxyeicosatetraenoic acid (disambiguation)|hydroxyeicosatetraenoic acids]] (HETEs) and [[epoxyeicosatrienoic acid]]s (EETs) by [[epoxygenase]].<ref name=boron108>{{cite book |author=Walter F., PhD. Boron |title=Medical Physiology: A Cellular And Molecular Approaoch |publisher=Elsevier/Saunders |year=2003 |page=108 |isbn=1-4160-2328-3}}</ref>


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.
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> activation===
===PLA<sub>2</sub> activation===
Line 136: Line 131:
==In the body==
==In the body==


===Muscle growth===
===Cell membranes===
Along with other omega-6 and omega-3 fatty acids, arachidonic acid contributes to the structure of cell membranes.<ref name=lpi/> When incorporated into [[phospholipid]]s, the omega fatty acids affect cell membrane properties, such as permeability and the activity of enzymes and cell-signaling mechanisms.<ref name=lpi/>
Arachidonic acid promotes the repair and growth of skeletal muscle tissue via conversion to prostaglandin [[PGF2alpha]] during and following [[physical exercise]].<ref name="Skeletal muscle COX review 2013">{{cite journal | vauthors = Trappe TA, Liu SZ | title = Effects of prostaglandins and COX-inhibiting drugs on skeletal muscle adaptations to exercise | journal = J. Appl. Physiol. | volume = 115 | issue = 6 | pages = 909–19 | year= 2013 | pmid = 23539318 | pmc = 3764617 | doi = 10.1152/japplphysiol.00061.2013 }}</ref> PGF2alpha promotes muscle protein synthesis by signaling through the [[Akt]]/[[mTOR]] pathway,<ref name="Skeletal muscle COX review 2013" /> similar to [[leucine]], [[β-hydroxy β-methylbutyric acid]] (HMB), and [[phosphatidic acid]]s.


===Brain===
===Brain===
Arachidonic acid is one of the most abundant fatty acids in the brain, and is present in similar quantities to [[docosahexaenoic acid]] (DHA). The two account for about 20% of its fatty-acid content.<ref>{{cite journal |last1=Crawford |first1=MA |last2=Sinclair |first2=AJ |title=Nutritional influences in the evolution of mammalian brain. In: lipids, malnutrition & the developing brain |journal=Ciba Foundation Symposium |pages=267–92 |year=1971 |doi=10.1002/9780470719862.ch16 |pmid=4949878}}</ref> Like DHA, neurological health is reliant upon sufficient levels of arachidonic acid. Among other things, arachidonic acid helps to maintain [[hippocampus|hippocampal]] cell membrane fluidity.<ref>{{Cite journal
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.<ref>{{cite journal |last1=Crawford |first1=MA |last2=Sinclair |first2=AJ |title=Nutritional influences in the evolution of mammalian brain. In: lipids, malnutrition & the developing brain |journal=Ciba Foundation Symposium |pages=267–92 |year=1971 |doi=10.1002/9780470719862.ch16 |pmid=4949878}}</ref> Arachidonic acid is involved in the early neurological development of infants.<ref name="crawford">{{cite journal |vauthors=Crawford MA, Sinclair AJ, Hall B, Ogundipe E, Wang Y, Bitsanis D, Djahanbakhch OB, Harbige L, Ghebremeskel K, Golfetto I, Moodley T, Hassam A, Sassine A, Johnson MR|display-authors=3 |title=The imperative of arachidonic acid in early human development |journal=Progress in Lipid Research |volume=91 |issue= |pages=101222 |date=July 2023 |pmid=36746351 |doi=10.1016/j.plipres.2023.101222 |doi-access=free }}</ref>
| doi = 10.1016/j.neurobiolaging.2006.05.023
| pmid = 16790296
| year = 2007
| last1 = Fukaya | first1 = T.
| last2 = Gondaira | first2 = T.
| last3 = Kashiyae | first3 = Y.
| last4 = Kotani | first4 = S.
| last5 = Ishikura | first5 = Y.
| last6 = Fujikawa | first6 = S.
| last7 = Kiso | first7 = Y.
| last8 = Sakakibara | first8 = M.
| title = Arachidonic acid preserves hippocampal neuron membrane fluidity in senescent rats
| volume = 28
| issue = 8
| pages = 1179–1186
| journal = Neurobiology of Aging
| s2cid = 11284462
}}</ref> It also helps protect the brain from oxidative stress by activating [[peroxisome proliferator-activated receptor gamma]].<ref>{{cite journal |last1=Wang |first1=ZJ |last2=Liang |first2=CL |last3=Li |first3=GM |last4=Yu |first4=CY |last5=Yin |first5=M |title=Neuroprotective effects of arachidonic acid against oxidative stress on rat hippocampal slices |journal=Chemico-Biological Interactions |volume=163 |issue=3 |pages=207–17 |year=2006 |pmid=16982041 |doi=10.1016/j.cbi.2006.08.005}}</ref> AA also activates [[syntaxin]]-3 (STX-3), a protein involved in the growth and repair of neurons.<ref>{{cite journal |last1=Darios |first1=F |last2=Davletov |first2=B |title=Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on syntaxin 3 |journal=Nature |volume=440 |issue=7085 |pages=813–7 |year=2006 |pmid=16598260 |doi=10.1038/nature04598 |bibcode=2006Natur.440..813D|s2cid=4411524 }}</ref>

Arachidonic acid is also involved in early neurological development. In one study<!-- funded by the U.S. National Institute of Child Health and Human Development -->, infants (18 months) given supplemental arachidonic acid for 17 weeks demonstrated significant improvements in intelligence, as measured by the Mental Development Index.<ref name="Developmental Medicine and Child Neurology, March 2000">{{cite journal | doi = 10.1111/j.1469-8749.2000.tb00066.x | title = A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants | year = 2007 | last1 = Birch | first1 = Eileen E | last2 = Garfield | first2 = Sharon | last3 = Hoffman | first3 = Dennis R | last4 = Uauy | first4 = Ricardo | last5 = Birch | first5 = David G | journal = Developmental Medicine & Child Neurology | volume = 42 | issue = 3 | pages = 174–181| pmid = 10755457 | s2cid = 30740256 }}</ref> This effect is further enhanced by the simultaneous supplementation of AA with DHA.

In adults, the disturbed metabolism of AA may contribute to neuropsychiatric disorders such as [[Alzheimer's disease]] and [[bipolar disorder]].<ref>{{cite journal |last1=Rapoport |first1=SI |title=Arachidonic acid and the brain |journal=The Journal of Nutrition |volume=138 |issue=12 |pages=2515–20 |year=2008 |doi=10.1093/jn/138.12.2515 |pmid=19022981 |pmc=3415870}}</ref> There is evidence of significant alterations in the conversion of arachidonic acid to other bioactive molecules (overexpression or disturbances in the AA enzyme cascade) in these conditions.

===Alzheimer's disease===
Studies on arachidonic acid and the pathogenesis of Alzheimer's disease have shown mixed results, with one study of ' and its metabolites that suggests they are associated with the onset of Alzheimer's disease,<ref>{{Cite journal
| last1 = Amtul | first1 = Z.
| last2 = Uhrig | first2 = M.
| last3 = Wang | first3 = L.
| last4 = Rozmahel | first4 = R. F.
| last5 = Beyreuther | first5 = K.
| title = Detrimental effects of arachidonic acid and its metabolites in cellular and mouse models of Alzheimer's disease: Structural insight
| doi = 10.1016/j.neurobiolaging.2011.07.014
| journal = Neurobiology of Aging
| volume = 33
| issue = 4
| pages = 831.e21–31
| year = 2012
| pmid = 21920632
| s2cid = 40458276
}}</ref> whereas another study suggests that the supplementation of arachidonic acid during the early stages of this disease may be effective in reducing symptoms and slowing the disease progress.<ref>{{cite journal |last1=Schaeffer |first1=EL |last2=Forlenza |first2=OV |last3=Gattaz |first3=WF |title=Phospholipase A2 activation as a therapeutic approach for cognitive enhancement in early-stage Alzheimer disease |journal=Psychopharmacology |volume=202 |issue=1–3 |pages=37–51 |year=2009 |pmid=18853146 |doi=10.1007/s00213-008-1351-0|s2cid=22940824 }}</ref> Additional studies on arachidonic acid supplementation for Alzheimer's patients are needed. Another study indicates that air pollution is the source of inflammation and arachidonic acid metabolites promote the inflammation to signal the immune system of the cell damage.<ref>{{Cite journal
| pmid = 15513908
| year = 2004
| last1 = Calderón-Garcidueñas
| first1 = L
| last2 = Reed
| first2 = W
| last3 = Maronpot
| first3 = R. R.
| last4 = Henríquez-Roldán
| first4 = C
| last5 = Delgado-Chavez
| first5 = R
| last6 = Calderón-Garcidueñas
| first6 = A
| last7 = Dragustinovis
| first7 = I
| last8 = Franco-Lira
| first8 = M
| last9 = Aragón-Flores
| first9 = M
| last10 = Solt
| first10 = A. C.
| last11 = Altenburg
| first11 = M
| last12 = Torres-Jardón
| first12 = R
| last13 = Swenberg
| first13 = J. A.
| title = Brain inflammation and Alzheimer's-like pathology in individuals exposed to severe air pollution
| volume = 32
| issue = 6
| pages = 650–8
| doi = 10.1080/01926230490520232
| journal = Toxicologic Pathology
| s2cid = 22802202
}}</ref>

===Bodybuilding supplement===
Arachidonic acid is marketed as an [[anabolic]] [[bodybuilding supplement]] in a variety of products. Supplementation of arachidonic acid (1,500&nbsp;mg/day for eight weeks) has been shown to increase lean body mass, strength, and anaerobic power in experienced resistance-trained men. This was demonstrated in a placebo-controlled study at the University of Tampa. Thirty men (aged 20.4 ± 2.1 years) took arachidonic acid or a placebo for eight weeks, and participated in a controlled resistance-training program. After eight weeks, lean body mass (LBM) had increased significantly, and to a greater extent, in the AA group (1.62&nbsp;kg) vs. placebo (0.09&nbsp;kg) (p<0.05). The change in muscle thickness was also greater in the AA group (.47&nbsp;cm) than placebo (.25&nbsp;cm) (p<0.05). Wingate anaerobic power increased to a greater extent in AA group as well (723.01 to 800.66 W) vs. placebo (738.75 to 766.51 W). Lastly, the change in total strength was significantly greater in the AA group (109.92&nbsp;lbs.) compared to placebo (75.78&nbsp;lbs.). These results suggest that AA supplementation can positively augment adaptations in strength and skeletal muscle hypertrophy in resistance-trained men.<ref>{{cite web|last1=Ormes|first1=Jacob|title=Effects of Arachidonic Acid Supplementation on Skeletal Muscle Mass, Strength, and Power|url=http://www.eventscribe.com/2014/posters/nsca/SplitViewer.asp?PID=NzkzNjA1MjQx|website=NSCA ePoster Gallery|publisher=National Strength and Conditioning Association|access-date=2014-08-22|archive-url=https://web.archive.org/web/20180909160613/http://www.eventscribe.com/2014/posters/nsca/SplitViewer.asp?PID=NzkzNjA1MjQx|archive-date=2018-09-09|url-status=dead}}</ref>

An earlier clinical study examining the effects of 1,000&nbsp;mg/day of arachidonic acid for 50 days found supplementation to enhance anaerobic capacity and performance in exercising men. During this study, a significant group–time interaction effect was observed in Wingate relative peak power (AA: 1.2 ± 0.5; P: -0.2 ± 0.2 W•kg-1, p=0.015). Statistical trends were also seen in bench press 1RM (AA: 11.0 ± 6.2; P: 8.0 ± 8.0&nbsp;kg, p=0.20), Wingate average power (AA:37.9 ± 10.0; P: 17.0 ± 24.0 W, p=0.16), and Wingate total work (AA: 1292 ± 1206; P: 510 ± 1249 J, p=0.087). AA supplementation during resistance training promoted significant increases in relative peak power with other performance-related variables approaching significance. These findings support the use of AA as an ergogenic.<ref>{{cite journal |last1=Roberts |first1=MD |last2=Iosia |first2=M |last3=Kerksick |first3=CM |last4=Taylor |first4=LW |last5=Campbell |first5=B |last6=Wilborn |first6=CD |last7=Harvey |first7=T |last8=Cooke |first8=M |last9=Rasmussen |first9=C |title=Effects of arachidonic acid supplementation on training adaptations in resistance-trained males |journal=Journal of the International Society of Sports Nutrition |volume=4 |pages=21 |year=2007 |pmid=18045476 |pmc=2217562 |doi=10.1186/1550-2783-4-21 |last10=Greenwood |first10=Mike |last11=Wilson |first11=Ronald |last12=Jitomir |first12=Jean |last13=Willoughby |first13=Darryn |last14=Kreider |first14=Richard B}}</ref>

==Dietary arachidonic acid and inflammation==
Increased consumption of arachidonic acid will not cause inflammation during normal metabolic conditions unless [[lipid peroxidation]] products are mixed in. Arachidonic acid is metabolized to both proinflammatory and anti-inflammatory eicosanoids during and after the inflammatory response, respectively. Arachidonic acid is also metabolized to inflammatory and anti-inflammatory eicosanoids during and after physical activity to promote growth. However, chronic inflammation from exogenous toxins and [[Physical exercise#Excessive exercise|excessive exercise]] should not be confused with acute inflammation from exercise and sufficient rest that is required by the inflammatory response to promote the repair and growth of the micro tears of tissues.<ref name =Harris>{{cite journal |last1=Harris |first1=WS |last2=Mozaffarian |first2=D |last3=Rimm |first3=E |last4=Kris-Etherton |first4=P |last5=Rudel |first5=LL |last6=Appel |first6=LJ |last7=Engler |first7=MM |last8=Engler |first8=MB |last9=Sacks |first9=F |title=Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention |journal=Circulation |volume=119 |issue=6 |pages=902–7 |year=2009 |pmid=19171857 |doi=10.1161/CIRCULATIONAHA.108.191627|doi-access=free }}</ref> However, the evidence is mixed. Some studies giving between 840&nbsp;mg and 2,000&nbsp;mg per day to healthy individuals for up to 50 days have shown no increases in inflammation or related metabolic activities.<ref name=Harris/><ref name=Nelson97>{{cite journal |doi=10.1007/s11745-997-0055-7 |last1=Nelson |first1=GJ |last2=Schmidt |first2=PC |last3=Bartolini |first3=G |last4=Kelley |first4=DS |last5=Kyle |first5=D |title=The effect of dietary arachidonic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans |journal=Lipids |volume=32 |pmid=9113631 |issue=4 |pages=421–5 |year=1997|s2cid=4053608 }}</ref><ref name=Wilborn>[http://arachidonic.com/ARA-baylorsafety.pdf Changes in whole blood and clinical safety markers over 50 days of concomitant arachidonic acid supplementation and resistance training] {{Webarchive|url=https://web.archive.org/web/20110707154713/http://arachidonic.com/ARA-baylorsafety.pdf |date=2011-07-07 }}. Wilborn, C, M Roberts, C Kerksick, M Iosia, L Taylor, B Campbell, T Harvey, R Wilson, M. Greenwood, D Willoughby and R Kreider. Proceedings of the International Society of Sports Nutrition (ISSN) Conference June 15–17, 2006.</ref><ref>{{cite journal |last1=Pantaleo |first1=P |last2=Marra |first2=F |last3=Vizzutti |first3=F |last4=Spadoni |first4=S |last5=Ciabattoni |first5=G |last6=Galli |first6=C |last7=La Villa |first7=G |last8=Gentilini |first8=P |last9=Laffi |first9=G |title=Effects of dietary supplementation with arachidonic acid on platelet and renal function in patients with cirrhosis |journal=Clinical Science |volume=106 |issue=1 |pages=27–34 |year=2004 |pmid=12877651 |doi=10.1042/CS20030182}}</ref> However, others show that increased arachidonic acid levels are actually associated with reduced pro-inflammatory IL-6 and IL-1 levels and increased anti-inflammatory [[tumor necrosis factor-beta]].<ref>{{cite journal |last1=Ferrucci |first1=L |last2=Cherubini |first2=A |last3=Bandinelli |first3=S |last4=Bartali |first4=B |last5=Corsi |first5=A |last6=Lauretani |first6=F |last7=Martin |first7=A |last8=Andres-Lacueva |first8=C |last9=Senin |first9=U |title=Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers |journal=The Journal of Clinical Endocrinology and Metabolism |volume=91 |issue=2 |pages=439–46 |year=2006 |pmid=16234304 |doi=10.1210/jc.2005-1303 |last10=Guralnik |first10=JM|doi-access=free }}</ref> This may result in a reduction in systemic inflammation.{{mcn|date=May 2017}}

Arachidonic acid does still play a central role in inflammation related to injury and many diseased states. How it is metabolized in the body dictates its inflammatory or anti-inflammatory activity. Individuals suffering from joint pains or active inflammatory disease may find that increased arachidonic acid consumption exacerbates symptoms, presumably because it is being more readily converted to inflammatory compounds.{{mcn|date=May 2017}} Likewise, high arachidonic acid consumption is not advised for individuals with a history of inflammatory disease, or who are in compromised health. Of note, while AA supplementation does not appear to have proinflammatory effects in healthy individuals, it may counter the anti-inflammatory effects of [[omega-3 fatty acid]] supplementation.<ref>{{cite journal |last1=Li |first1=B |last2=Birdwell |first2=C |last3=Whelan |first3=J |title=Antithetic relationship of dietary arachidonic acid and eicosapentaenoic acid on eicosanoid production in vivo |journal=Journal of Lipid Research |volume=35 |issue=10 |pages=1869–77 |year=1994 |doi=10.1016/S0022-2275(20)39782-0 |pmid=7852864|doi-access=free }}</ref>

==Health effects of arachidonic acid supplementation==
Arachidonic acid supplementation in daily doses of 1,000–1,500&nbsp;mg for 50 days has been well tolerated during several clinical studies, with no significant side effects reported. All common markers of health, including kidney and liver function,<ref name=Wilborn/> serum lipids,<ref>{{cite journal |last1=Nelson |doi=10.1007/s11745-997-0056-6 |first1=GJ |last2=Schmidt |first2=PC |last3=Bartolini |first3=G |last4=Kelley |first4=DS |last5=Phinney |first5=SD |last6=Kyle |first6=D |last7=Silbermann |first7=S |last8=Schaefer |first8=EJ |title=The effect of dietary arachidonic acid on plasma lipoprotein distributions, apoproteins, blood lipid levels, and tissue fatty acid composition in humans |journal=Lipids |volume=32 |pmid=9113632 |issue=4 |pages=427–33 |year=1997|s2cid=4056220 }}</ref> immunity,<ref>{{cite journal |doi=10.1007/s11745-998-0187-9 |last1=Kelley |first1=DS |last2=Taylor |first2=PC |last3=Nelson |first3=GJ |last4=MacKey |first4=BE |title=Arachidonic acid supplementation enhances synthesis of eicosanoids without suppressing immune functions in young healthy men |journal=Lipids |pmid=9507233 |volume=33 |issue=2 |pages=125–30 |year=1998|s2cid=3970315 |url=https://zenodo.org/record/1232866 }}</ref> and platelet aggregation<ref name=Nelson97/> appear to be unaffected with this level and duration of use. Furthermore, higher concentrations of AA in muscle tissue may be correlated with improved insulin sensitivity.<ref>{{cite journal |last1=Borkman |first1=M |last2=Storlien |first2=LH |last3=Pan |first3=DA |last4=Jenkins |first4=AB |last5=Chisholm |first5=DJ |last6=Campbell |first6=LV |title=The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids |journal=The New England Journal of Medicine |volume=328 |issue=4 |pages=238–44 |year=1993 |pmid=8418404 |doi=10.1056/NEJM199301283280404}}</ref> Arachidonic acid supplementation of the diets of healthy adults appears to offer no toxicity or significant safety risk.

While studies looking at arachidonic acid supplementation in sedentary subjects have failed to find changes in resting inflammatory markers in doses up to 1,500&nbsp;mg daily, strength-trained subjects may respond differently. One study <!-- at Baylor University --> reported a significant reduction in resting inflammation (via marker IL-6) in young men supplementing 1,000&nbsp;mg/day of arachidonic acid for 50 days in combination with resistance training. This suggests that rather being pro-inflammatory, supplementation of AA while undergoing resistance training may actually improve the regulation of systemic inflammation.<ref>{{cite journal|last1=Roberts|first1=MD|last2=Iosia|first2=M|last3=Kerksick|first3=CM|last4=Taylor|first4=LW|last5=Campbell|first5=B|last6=Wilborn|first6=CD|last7=Harvey|first7=T|last8=Cooke|first8=M|last9=Rasmussen|first9=C|last10=Greenwood|first10=M|last11=Wilson|first11=R|last12=Jitomir|first12=J|last13=Willoughby|first13=D|last14=Kreider|first14=RB|title=Effects of arachidonic acid supplementation on training adaptations in resistance-trained males.|journal=Journal of the International Society of Sports Nutrition|date=Nov 28, 2007|volume=4|pages=21|pmid=18045476|doi=10.1186/1550-2783-4-21|pmc=2217562}}</ref>


==Dietary supplement==
A meta-analysis <!-- by Cambridge University --> looking for associations between heart disease risk and individual fatty acids reported a significantly reduced risk of heart disease with higher levels of EPA and DHA (omega-3 fats), as well as the omega-6 arachidonic acid.<ref>{{cite journal|last1=Chowdhury|first1=R|last2=Warnakula|first2=S|last3=Kunutsor|first3=S|last4=Crowe|first4=F|last5=Ward|first5=HA|last6=Johnson|first6=L|last7=Franco|first7=OH|last8=Butterworth|first8=AS|last9=Forouhi|first9=NG|last10=Thompson|first10=SG|last11=Khaw|first11=KT|last12=Mozaffarian|first12=D|last13=Danesh|first13=J|last14=Di Angelantonio|first14=E|title=Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis.|journal=Annals of Internal Medicine|date=Mar 18, 2014|volume=160|issue=6|pages=398–406|pmid=24723079|doi=10.7326/M13-1788}}</ref> A scientific advisory from the American Heart Association has also favorably evaluated the health impact of dietary omega-6 fats, including arachidonic acid.<ref name=Harris /> The group does not recommend limiting this essential fatty acid. In fact, the paper recommends individuals follow a diet that consists of at least 5–10% of calories coming from omega-6 fats, including arachidonic acid. It suggests dietary AA is not a risk factor for heart disease, and may play a role in maintaining optimal metabolism and reduced heart disease risk. Maintaining sufficient intake levels of both omega-3 and omega-6 fatty acids, therefore, is recommended for optimal health.
Arachidonic acid is marketed as a [[dietary supplement]].<ref name=lpi/><ref name=ods/> 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.<ref name="calder">{{cite journal |vauthors=Calder PC, Campoy C, Eilander A, Fleith M, Forsyth S, Larsson PO, Schelkle B, Lohner S, Szommer A, van de Heijning BJ, Mensink RP |title=A systematic review of the effects of increasing arachidonic acid intake on PUFA status, metabolism and health-related outcomes in humans |journal=The British Journal of Nutrition |volume=121 |issue=11 |pages=1201–1214 |date=June 2019 |pmid=31130146 |doi=10.1017/S0007114519000692 |url=https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/systematic-review-of-the-effects-of-increasing-arachidonic-acid-intake-on-pufa-status-metabolism-and-healthrelated-outcomes-in-humans/6A0167CBF8EC148B4855C25D002E4AC4 |hdl=10481/60184 |hdl-access=free }}</ref> There were no [[adverse effect]]s in adults of using high daily doses (1500 mg) of arachidonic acid on several [[biomarker]]s of [[Clinical chemistry|blood chemistry]], [[immune function]], and [[inflammation]].<ref name=calder/>


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 disease]]s compared to lower intakes.<ref name =Harris>{{cite journal |last1=Harris |first1=WS |last2=Mozaffarian |first2=D |last3=Rimm |first3=E |last4=Kris-Etherton |first4=P |last5=Rudel |first5=LL |last6=Appel |first6=LJ |last7=Engler |first7=MM |last8=Engler |first8=MB |last9=Sacks |first9=F |title=Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention |journal=Circulation |volume=119 |issue=6 |pages=902–7 |year=2009 |pmid=19171857 |doi=10.1161/CIRCULATIONAHA.108.191627 |doi-access=|s2cid=15072227|url=https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.108.191627}}</ref> 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.<ref>{{cite journal |last1=Chowdhury |first1=R |last2=Warnakula |first2=S |last3=Kunutsor |first3=S |last4=Crowe |first4=F |last5=Ward |first5=HA |last6=Johnson |first6=L |last7=Franco |first7=OH |last8=Butterworth |first8=AS |last9=Forouhi |first9=NG|last10=Thompson|first10=SG |last11=Khaw |first11=KT |last12=Mozaffarian |first12=D |last13=Danesh |first13=J |last14=Di Angelantonio |first14=E |title=Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis. |journal=Annals of Internal Medicine |date=Mar 18, 2014 |volume=160 |issue=6 |pages=398–406 |pmid=24723079 |doi=10.7326/M13-1788}}</ref>
Arachidonic acid is not [[carcinogen]]ic, and studies show dietary level is not associated (positively or negatively) with risk of cancers.<ref>{{cite journal |last1=Schuurman |first1=AG |last2=Van Den Brandt |first2=PA |last3=Dorant |first3=E |last4=Brants |first4=HA |last5=Goldbohm |first5=RA |title=Association of energy and fat intake with prostate carcinoma risk: results from The Netherlands Cohort Study |journal=Cancer |volume=86 |issue=6 |pages=1019–27 |year=1999 |pmid=10491529 |doi=10.1002/(SICI)1097-0142(19990915)86:6<1019::AID-CNCR18>3.0.CO;2-H|url=https://cris.maastrichtuniversity.nl/en/publications/e40039e2-ad3d-4c6f-95a8-3c76fc888dc3 |doi-access=free }}</ref><ref>{{cite journal |last1=Leitzmann |first1=MF |last2=Stampfer |first2=MJ |last3=Michaud |first3=DS |last4=Augustsson |first4=K |last5=Colditz |first5=GC |last6=Willett |first6=WC |last7=Giovannucci |first7=EL |title=Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer |journal=The American Journal of Clinical Nutrition |volume=80 |issue=1 |pages=204–16 |year=2004 |doi=10.1093/ajcn/80.1.204 |pmid=15213050|doi-access=free }}</ref><ref>{{cite journal |last1=Astorg |first1=P |title=Dietary fatty acids and colorectal and prostate cancers: epidemiological studies |journal=Bulletin du cancer |volume=92 |issue=7 |pages=670–84 |year=2005 |pmid=16123006}}</ref><ref>{{cite journal |last1=Whelan |first1=J |last2=McEntee |first2=MF |title=Dietary (n-6) PUFA and intestinal tumorigenesis |journal=The Journal of Nutrition |volume=134 |issue=12 Suppl |pages=3421S–3426S |year=2004 |doi=10.1093/jn/134.12.3421S |pmid=15570048|doi-access=free }}</ref> AA remains integral to the inflammatory and cell growth process, however, which is disturbed in many types of disease including cancer. Therefore, the safety of arachidonic acid supplementation in patients suffering from cancer, inflammatory, or other diseased states is unknown, and supplementation is not recommended.


==See also==
==See also==
Line 243: Line 148:
* [[Fish oil]]
* [[Fish oil]]
* [[Polyunsaturated fat]]
* [[Polyunsaturated fat]]
* [[Polyunsaturated fatty acid]]
{{div col end}}
{{div col end}}
<!-- please keep entries in alphabetical order -->
<!-- please keep entries in alphabetical order -->


==References==
==References==
{{reflist|30em}}
{{reflist}}


==External links==
==External links==
* [https://web.archive.org/web/20060715122827/http://www.acnp.org/g4/GN401000059/Default.htm Arachidonic Acid] at acnp.org
* {{MeshName|Arachidonic+Acid}}
* {{MeshName|Arachidonic+Acid}}


Latest revision as of 21:15, 28 July 2024

Arachidonic acid
Structural formula of arachidonic acid
Names
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)
3DMet
1713889
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.007.304 Edit this at Wikidata
EC Number
  • 208-033-4
58972
KEGG
MeSH Arachidonic+acid
RTECS number
  • CE6675000
UNII
  • InChI=1S/C20H32O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20(21)22/h6-7,9-10,12-13,15-16H,2-5,8,11,14,17-19H2,1H3,(H,21,22) ☒N
    Key: YZXBAPSDXZZRGB-UHFFFAOYSA-N ☒N
  • InChI=1S/C20H32O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20(21)22/h6-7,9-10,12-13,15-16H,2-5,8,11,14,17-19H2,1H3,(H,21,22)/b7-6-,10-9-,13-12-,16-15-
  • Key: YZXBAPSDXZZRGB-DOFZRALJSA-N
  • CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCCC(=O)O
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)
NFPA 704 four-colored diamondHealth 1: Exposure would cause irritation but only minor residual injury. E.g. turpentineFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
1
1
0
Flash point 113 °C (235 °F; 386 K)
Related compounds
Related compounds
 Eicosatetraenoic acid
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

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] If its precursors or diet contains linoleic acid it is formed by biosynthesis and can be deposited in animal fats. 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', but 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

[edit]

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]

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

[edit]
Eicosanoid synthesis

Arachidonic acid is freed from phospholipid 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 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]
Further information: Phospholipase A2 § Regulation

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]
Further information: Phospholipase C § 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.[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]

Cell membranes

[edit]

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]

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]

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]

References

[edit]
  1. ^ Pubchem. "5,8,11,14-Eicosatetraenoic acid | C20H32O2 - PubChem". pubchem.ncbi.nlm.nih.gov. Retrieved 2016-03-31.
  2. ^ a b c d e "Essential fatty acids". Micronutrient Information Center, Linus Pauling Institute, Oregon State University. June 2019. Retrieved 13 May 2024.
  3. ^ "IUPAC Lipid nomenclature: Appendix A: names of and symbols for higher fatty acids". www.sbcs.qmul.ac.uk.
  4. ^ "Dorland's Medical Dictionary – 'A'". Archived from the original on 11 January 2007. Retrieved 2007-01-12.
  5. ^ a b "Omega-3 fatty acids". Office of Dietary Supplements, US National Institutes of Health. 15 February 2023. Retrieved 13 May 2024.
  6. ^ Truswell A, Choudhury N, Peterson D, Mann J, Agostoni C, Riva E, Giovannini M, Marangoni F, Galli C (1994). "Arachidonic acid and peanut oil". The Lancet. 344 (8928): 1030–1031. doi:10.1016/S0140-6736(94)91695-0. PMID 7999151. S2CID 1522233.
  7. ^ Smith GI, Atherton P, Reeds DN, Mohammed BS, Rankin D, Rennie MJ, Mittendorfer B (Sep 2011). "Omega-3 polyunsaturated fatty acids augment the muscle protein anabolic response to hyperinsulinaemia-hyperaminoacidaemia in healthy young and middle-aged men and women". Clinical Science. 121 (6): 267–78. doi:10.1042/cs20100597. PMC 3499967. PMID 21501117.
  8. ^ a b c Baynes JW, Marek H. Dominiczak (2005). Medical Biochemistry 2nd. Edition. Elsevier Mosby. p. 555. ISBN 0-7234-3341-0.
  9. ^ Wlodawer P, Samuelsson B (1973). "On the organization and mechanism of prostaglandin synthetase". The Journal of Biological Chemistry. 248 (16): 5673–8. doi:10.1016/S0021-9258(19)43558-8. PMID 4723909.
  10. ^ 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. PMID 12432913.
  11. ^ Powell WS, Rokach J (Apr 2015). "Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid". Biochim Biophys Acta. 1851 (4): 340–355. doi:10.1016/j.bbalip.2014.10.008. PMC 5710736. PMID 25449650.
  12. ^ Brash AR, Boeglin WE, Chang MS (Jun 1997). "Discovery of a second 15S-lipoxygenase in humans". Proc Natl Acad Sci U S A. 94 (12): 6148–52. Bibcode:1997PNAS...94.6148B. doi:10.1073/pnas.94.12.6148. PMC 21017. PMID 9177185.
  13. ^ Zhu D, Ran Y (May 2012). "Role of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in hypoxia-induced pulmonary hypertension". J Physiol Sci. 62 (3): 163–72. doi:10.1007/s12576-012-0196-9. PMC 10717549. PMID 22331435. S2CID 2723454.
  14. ^ 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. PMID 25895638.
  15. ^ Feltenmark S, Gautam N, Brunnström A, Griffiths W, Backman L, Edenius C, Lindbom L, Björkholm M, Claesson HE (Jan 2008). "Eoxins are proinflammatory arachidonic acid metabolites produced via the 15-lipoxygenase-1 pathway in human eosinophils and mast cells". Proc Natl Acad Sci U S A. 105 (2): 680–5. Bibcode:2008PNAS..105..680F. doi:10.1073/pnas.0710127105. PMC 2206596. PMID 18184802.
  16. ^ 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. PMID 24685839.
  17. ^ Ueda N, Tsuboi K, Uyama T (May 2013). "Metabolism of endocannabinoids and related N -acylethanolamines: Canonical and alternative pathways". FEBS J. 280 (9): 1874–94. doi:10.1111/febs.12152. PMID 23425575. S2CID 205133026.
  18. ^ Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 108. ISBN 1-4160-2328-3.
  19. ^ a b c d e f Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 103. ISBN 1-4160-2328-3.
  20. ^ a b c d e f Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 104. ISBN 1-4160-2328-3.
  21. ^ 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. PMID 4949878.
  22. ^ Crawford MA, Sinclair AJ, Hall B, et al. (July 2023). "The imperative of arachidonic acid in early human development". Progress in Lipid Research. 91: 101222. doi:10.1016/j.plipres.2023.101222. PMID 36746351.
  23. ^ a b Calder PC, Campoy C, Eilander A, Fleith M, Forsyth S, Larsson PO, Schelkle B, Lohner S, Szommer A, van de Heijning BJ, Mensink RP (June 2019). "A systematic review of the effects of increasing arachidonic acid intake on PUFA status, metabolism and health-related outcomes in humans". The British Journal of Nutrition. 121 (11): 1201–1214. doi:10.1017/S0007114519000692. hdl:10481/60184. PMID 31130146.
  24. ^ Harris WS, Mozaffarian D, Rimm E, Kris-Etherton P, Rudel LL, Appel LJ, Engler MM, Engler MB, Sacks F (2009). "Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention". Circulation. 119 (6): 902–7. doi:10.1161/CIRCULATIONAHA.108.191627. PMID 19171857. S2CID 15072227.
  25. ^ Chowdhury R, Warnakula S, Kunutsor S, Crowe F, Ward HA, Johnson L, Franco OH, Butterworth AS, Forouhi NG, Thompson SG, Khaw KT, Mozaffarian D, Danesh J, Di Angelantonio E (Mar 18, 2014). "Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis". Annals of Internal Medicine. 160 (6): 398–406. doi:10.7326/M13-1788. PMID 24723079.
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