Docosanoid
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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. 4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid) by lipoxygenase, cyclooxygenase, and cytochrome P450 enzymes. Other docosanoids are metabolites of n-3 docosapentaenoic acid (DPA) (i.e. 7Z,10Z,13Z,16Z,19Z-docosapentaenoic acid, or clupanodonic acid), n-6 DPA (i.e. 4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid, or osbond acid), and docosatetraenoic acid (i.e. 7Z,10Z,13Z,16Z-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.
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 (RvD1n-3, RvD2n-3, and RvD5n-3) 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: PD1n-3 and PD2n-3.
- DHA-derived maresins: MaR1, MaR2, 7-epi-Mar1, Mar-L1, and Mar-L2.
- n-3 DPA-derived maresins: Mar1n-3, Mar2n-3, and Mar3n-3.
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.[1][2][3][4]
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-Fαneuroprostane 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.[5][6]
Hydroxy-docosanoids
Cells metabolize DHA to 17S-hydroperoxy-4Z,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid (17-HpDHA) and then rapidly reduce this hydroperoxide to 17S-hydroxy-4Z,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid (17-HDHA) and similarly metabolize DHA to 13S-hydroperoxy-4Z,7Z,10Z,14Z,16Z,19Z-docosahexaenoic acid (13-HpDHA) and then to 13S-hydroxy-4Z,7Z,10Z,14Z,16Z,19Z-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.[7][8] Other SPM docosanoids, e.g. RvD1 and RvD2, have anti-growth effects against cancer cells in animal models.[9]
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 Specialized proresolving mediators § Oxo-DHA and oxo-DPA metabolites).[10]
DTA-derived docosanoids
Cyclooxygenase and cytochrome P450 oxidase act upon docosatetraenoic acid to produce dihomoprostaglandins,[11] dihomo-epoxyeicosatrienoic acids,[12] and dihomo-EETs.[13]
References
- ↑ Calder PC (2015). "Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1851 (4): 469–84. doi:10.1016/j.bbalip.2014.08.010. PMID 25149823.
- ↑ Serhan CN, Chiang N, Dalli J, Levy BD (2015). "Lipid mediators in the resolution of inflammation". Cold Spring Harbor Perspectives in Biology. 7 (2) a016311. doi:10.1101/cshperspect.a016311. PMC 4315926. PMID 25359497.
- ↑ Barden AE, Mas E, Mori TA (2016). "n-3 Fatty acid supplementation and proresolving mediators of inflammation". Current Opinion in Lipidology. 27 (1): 26–32. doi:10.1097/MOL.0000000000000262. PMID 26655290. S2CID 45820130.
- ↑ Balas L, Durand T (2016). "Dihydroxylated E,E,Z-docosatrienes. An overview of their synthesis and biological significance". Progress in Lipid Research. 61: 1–18. doi:10.1016/j.plipres.2015.10.002. PMID 26545300.
- ↑ Arneson KO, Roberts LJ (2007). "Measurement of products of docosahexaenoic acid peroxidation, neuroprostanes, and neurofurans". Lipidomics and Bioactive Lipids: Specialized Analytical Methods and Lipids in Disease. Methods in Enzymology. Vol. 433. pp. 127–43. doi:10.1016/S0076-6879(07)33007-3. ISBN 978-0-12-373966-7. PMID 17954232.
- ↑ Leung KS, Galano JM, Durand T, Lee JC (2015). "Current development in non-enzymatic lipid peroxidation products, isoprostanoids and isofuranoids, in novel biological samples". Free Radical Research. 49 (7): 816–26. doi:10.3109/10715762.2014.960867. PMID 25184341. S2CID 34479417.
- ↑ Chiu CY, Gomolka B, Dierkes C, Huang NR, Schroeder M, Purschke M, Manstein D, Dangi B, Weylandt KH (2012). "Omega-6 docosapentaenoic acid-derived resolvins and 17-hydroxydocosahexaenoic acid modulate macrophage function and alleviate experimental colitis". Inflammation Research. 61 (9): 967–76. doi:10.1007/s00011-012-0489-8. PMID 22618200. S2CID 18265905.
- ↑ O'Flaherty JT, Hu Y, Wooten RE, Horita DA, Samuel MP, Thomas MJ, Sun H, Edwards IJ (2012). "15-lipoxygenase metabolites of docosahexaenoic acid inhibit prostate cancer cell proliferation and survival". PLOS ONE. 7 (9) e45480. Bibcode:2012PLoSO...745480O. doi:10.1371/journal.pone.0045480. PMC 3447860. PMID 23029040.
- ↑ Serhan CN, Chiang N, Dalli J (2015). "The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution". Seminars in Immunology. 27 (3): 200–15. doi:10.1016/j.smim.2015.03.004. PMC 4515371. PMID 25857211.
- ↑ Weylandt KH (2015). "Docosapentaenoic acid derived metabolites and mediators - The new world of lipid mediator medicine in a nutshell". European Journal of Pharmacology. 785: 108–115. doi:10.1016/j.ejphar.2015.11.002. PMID 26546723.
- ↑ Campbell WB, Falck JR, Okita JR, Johnson AR, Callahan KS (1985). "Synthesis of dihomoprostaglandins from adrenic acid (7,10,13,16-docosatetraenoic acid) by human endothelial cells". Biochim. Biophys. Acta. 837 (1): 67–76. doi:10.1016/0005-2760(85)90086-4. PMID 3931686.
- ↑ Kopf PG, Zhang DX, Gauthier KM, Nithipatikom K, Yi XY, Falck JR, Campbell WB (2010). "Adrenic acid metabolites as endogenous endothelium-derived and zona glomerulosa-derived hyperpolarizing factors". Hypertension. 55 (2): 547–54. doi:10.1161/HYPERTENSIONAHA.109.144147. PMC 2819927. PMID 20038752.
- ↑ Yi XY, Gauthier KM, Cui L, Nithipatikom K, Falck JR, Campbell WB (May 2007). "Metabolism of adrenic acid to vasodilatory 1α,1β-dihomo-epoxyeicosatrienoic acids by bovine coronary arteries". Am J Physiol Heart Circ Physiol. 292 (5): H2265–74. doi:10.1152/ajpheart.00947.2006. PMID 17209008. S2CID 86090552.