{{Short description|Biologically active class of organic compounds}} In biochemistry, '''docosanoids''' are signaling molecules made by the metabolism of twenty-two-carbon fatty acids (EFAs), especially the omega-3 fatty acid, docosahexaenoic acid (DHA) (i.e. 4''Z'',7''Z'',10''Z'',13''Z'',16''Z'',19''Z''-docosahexaenoic acid) by lipoxygenase, cyclooxygenase, and cytochrome P450 enzymes. Other docosanoids are metabolites of n-3 docosapentaenoic acid (DPA) (i.e. 7''Z'',10''Z'',13''Z'',16''Z'',19''Z''-docosapentaenoic acid, or clupanodonic acid), n-6 DPA (i.e. 4''Z'',7''Z'',10''Z'',13''Z'',16''Z''-docosapentaenoic acid, or osbond acid), and docosatetraenoic acid (i.e. 7''Z'',10''Z'',13''Z'',16''Z''-docosatetraenoic acid, DTA, or adrenic acid). Prominent docosanoid metabolites of DPA and n-3 DHA are members of the specialized pro-resolving mediators class of polyunsaturated fatty acid metabolites that possess potent anti-inflammation, tissue healing, and other activities.
==Prominent docosanoids==
===Specialized proresolving mediator docosanoids=== Potently bioactive agents of the specialized proresolving mediator class include: * DHA-derived resolvins (Rvs) of the D series: RvD1, RvD2, RvD3, RvD4, RvD5, RvD6, AT-RvD1, AT-RvD2, AT-RvD3, AT-RvD4, AT-RvD5, and AT-RvD6. * n-3 DPA-derived resolvins of the D series (RvD1<sub>n-3</sub>, RvD2<sub>n-3</sub>, and RvD5<sub>n-3</sub>) and the T series (RvT1, RvT2, RvT3, and RvT4). * DHA-derived neuroprotectins, also termed protectins: PD1, PDX, 17-epi-PD1, and 10-epi-PD1. * n-3 DPA derived protectins: PD1<sub>n-3</sub> and PD2<sub>n-3</sub>. * DHA-derived maresins: MaR1, MaR2, 7-epi-Mar1, Mar-L1, and Mar-L2. * n-3 DPA-derived maresins: Mar1<sub>n-3</sub>, Mar2<sub>n-3</sub>, and Mar3<sub>n-3</sub>.
These DHA metabolites possess anti-inflammation and tissue-protection activities in animal models of inflammatory diseases; they are proposed to inhibit innate immune responses and thereby to protect from and to resolve a wide range of inflammatory responses in animals and humans. These metabolites are also proposed to contribute to the anti-inflammatory and other beneficial effects of dietary omega-3 fatty acids by being metabolized to them.<ref name="pmid25149823">{{cite journal | vauthors = Calder PC | title = Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance | journal = Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | volume = 1851 | issue = 4 | pages = 469–84 | year = 2015 | pmid = 25149823 | doi = 10.1016/j.bbalip.2014.08.010 }}</ref><ref name="pmid25359497">{{cite journal | vauthors = Serhan CN, Chiang N, Dalli J, Levy BD | title = Lipid mediators in the resolution of inflammation | journal = Cold Spring Harbor Perspectives in Biology | volume = 7 | issue = 2 | article-number = a016311 | year = 2015 | pmid = 25359497 | doi = 10.1101/cshperspect.a016311 | pmc=4315926}}</ref><ref name="pmid26655290">{{cite journal | vauthors = Barden AE, Mas E, Mori TA | title = n-3 Fatty acid supplementation and proresolving mediators of inflammation | journal = Current Opinion in Lipidology | volume = 27 | issue = 1 | pages = 26–32 | year = 2016 | pmid = 26655290 | doi = 10.1097/MOL.0000000000000262 | s2cid = 45820130 | url = https://api.research-repository.uwa.edu.au/files/26432732/N_3_Fatty_acid_supplementation_and_prorresolving_mediators_of_inflammation._AAM_ID_11273143.docx}}</ref><ref name="pmid26545300">{{cite journal | vauthors = Balas L, Durand T | title = Dihydroxylated E,E,Z-docosatrienes. An overview of their synthesis and biological significance | journal = Progress in Lipid Research | volume = 61 | pages = 1–18 | year = 2016 | pmid = 26545300 | doi = 10.1016/j.plipres.2015.10.002 }}</ref>
===Neurofuran docosanoids=== DHA can be converted non-enzymatically by free radical-mediated peroxidation to 8 different neurofuran regioisomers termed neuroprostanes and neurofuranes including 4-, 7-, 10-, 11-, 13-, 14-, 17-, and 20-series neurofurans/neuroporstanes for a total of 128 different racemic compounds. The most studied DHA-derived of these products are members of the 4-series, neurofuran 4-F<sub>α</sub>neuroprostane and 4(''RS'')-ST-Δ6-8-neurofurane. These metabolites have been used mainly as biomarkers of oxidative stress that are formed in nerve tissues of the central nervous system.<ref name="pmid17954232">{{cite book | vauthors = Arneson KO, Roberts LJ | title = Lipidomics and Bioactive Lipids: Specialized Analytical Methods and Lipids in Disease | chapter = Measurement of products of docosahexaenoic acid peroxidation, neuroprostanes, and neurofurans | series = Methods in Enzymology | volume = 433 | pages = 127–43 | year = 2007 | pmid = 17954232 | doi = 10.1016/S0076-6879(07)33007-3 | isbn = 978-0-12-373966-7 }}</ref><ref name="pmid25184341">{{cite journal | vauthors = Leung KS, Galano JM, Durand T, Lee JC | title = Current development in non-enzymatic lipid peroxidation products, isoprostanoids and isofuranoids, in novel biological samples | journal = Free Radical Research | volume = 49 | issue = 7 | pages = 816–26 | year = 2015 | pmid = 25184341 | doi = 10.3109/10715762.2014.960867 | s2cid = 34479417 }}</ref>
===Hydroxy-docosanoids=== Cells metabolize DHA to 17''S''-hydroperoxy-4''Z'',7''Z'',10''Z'',13''Z'',15''E'',19''Z''-docosahexaenoic acid (17-HpDHA) and then rapidly reduce this hydroperoxide to 17''S''-hydroxy-4''Z'',7''Z'',10''Z'',13''Z'',15''E'',19''Z''-docosahexaenoic acid (17-HDHA) and similarly metabolize DHA to 13''S''-hydroperoxy-4''Z'',7''Z'',10''Z'',14''Z'',16''Z'',19''Z''-docosahexaenoic acid (13-HpDHA) and then to 13''S''-hydroxy-4''Z'',7''Z'',10''Z'',14''Z'',16''Z'',19''Z''-docosahexaenoic acid (13-HDHA). 17-HDHA exhibits potent in vitro as well as in vivo (animal model) anti-inflammatory activity while 17-HpDHA and to a lesser extent 17-HDHA inhibit the growth of cultured human breast cancer cells.<ref name="pmid22618200">{{cite journal | vauthors = Chiu CY, Gomolka B, Dierkes C, Huang NR, Schroeder M, Purschke M, Manstein D, Dangi B, Weylandt KH | title = Omega-6 docosapentaenoic acid-derived resolvins and 17-hydroxydocosahexaenoic acid modulate macrophage function and alleviate experimental colitis | journal = Inflammation Research| volume = 61 | issue = 9 | pages = 967–76 | year = 2012 | pmid = 22618200 | doi = 10.1007/s00011-012-0489-8 | s2cid = 18265905 }}</ref><ref name="pmid23029040">{{cite journal | vauthors = O'Flaherty JT, Hu Y, Wooten RE, Horita DA, Samuel MP, Thomas MJ, Sun H, Edwards IJ | title = 15-lipoxygenase metabolites of docosahexaenoic acid inhibit prostate cancer cell proliferation and survival | journal = PLOS ONE | volume = 7 | issue = 9 | article-number = e45480 | year = 2012 | pmid = 23029040 | pmc = 3447860 | doi = 10.1371/journal.pone.0045480 | bibcode = 2012PLoSO...745480O | doi-access = free }}</ref> Other SPM docosanoids, e.g. RvD1 and RvD2, have anti-growth effects against cancer cells in animal models.<ref name="pmid25857211">{{cite journal | vauthors = Serhan CN, Chiang N, Dalli J | title = The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution | journal = Seminars in Immunology | volume = 27 | issue = 3 | pages = 200–15 | year = 2015 | pmid = 25857211 | pmc = 4515371 | doi = 10.1016/j.smim.2015.03.004 }}</ref>
===Oxo-docosanoids=== Cells can metabolize DHA to products that possess an oxo (i.e. ketone) residue. These products include 13-oxo-DHA (termed EFOXD6) and 17-oxo-DHA (termed 18-EFOXD6). Both oxo metabolites possess anti-inflammatory activity as assesses in in vitro systems (see {{slink|Specialized proresolving mediators|Oxo-DHA and oxo-DPA metabolites}}).<ref name="pmid26546723">{{cite journal | vauthors = Weylandt KH | title = Docosapentaenoic acid derived metabolites and mediators - The new world of lipid mediator medicine in a nutshell | journal = European Journal of Pharmacology | volume = 785| pages = 108–115| year = 2015 | pmid = 26546723 | doi = 10.1016/j.ejphar.2015.11.002 }}</ref>
===DTA-derived docosanoids=== Cyclooxygenase and cytochrome P450 oxidase act upon docosatetraenoic acid to produce dihomoprostaglandins,<ref name=Campbell>{{cite journal |vauthors=Campbell WB, Falck JR, Okita JR, Johnson AR, Callahan KS |author2-link=John R. Falck|title=Synthesis of dihomoprostaglandins from adrenic acid (7,10,13,16-docosatetraenoic acid) by human endothelial cells |journal=Biochim. Biophys. Acta |volume=837 |issue=1 |pages=67–76 |year=1985 |pmid=3931686 |doi=10.1016/0005-2760(85)90086-4}}</ref> dihomo-epoxyeicosatrienoic acids,<ref name="pmid20038752">{{cite journal | vauthors = Kopf PG, Zhang DX, Gauthier KM, Nithipatikom K, Yi XY, Falck JR, Campbell WB | title = Adrenic acid metabolites as endogenous endothelium-derived and zona glomerulosa-derived hyperpolarizing factors | journal = Hypertension |volume = 55 | issue = 2 | pages = 547–54 | year = 2010 | pmid = 20038752 | pmc = 2819927 | doi = 10.1161/HYPERTENSIONAHA.109.144147 }}</ref> and dihomo-EETs.<ref name=Yi>{{cite journal |journal=Am J Physiol Heart Circ Physiol |date =May 2007 |volume=292 |issue=5 |pages=H2265–74 |title=Metabolism of adrenic acid to vasodilatory 1α,1β-dihomo-epoxyeicosatrienoic acids by bovine coronary arteries |vauthors=Yi XY, Gauthier KM, Cui L, Nithipatikom K, Falck JR, Campbell WB |pmid=17209008 |doi=10.1152/ajpheart.00947.2006 |doi-access=free |s2cid=86090552}}</ref>
==References== {{reflist}}
Category:Docosanoids Category:Cell biology Category:Cell signaling Category:Cell communication Category:Biomolecules Category:Immunology Category:Fatty acids