Biology:Docosanoid

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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. 4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid) by lipoxygenase, cyclooxygenase, and cytochrome P450 enzymes. Other docosanoids are metabolites of n-3 docosapentaenoic acid (i.e. 7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid), n-6 DHA (i.e. 4Z,7Z,10Z,13Z,16Z-docosahexaenoic acid, and docosatetraenoic acid (i.e. 7Z,10Z,13Z,16Z-docosatetraenoic acid, DTA, or adrenic acid). Prominent docosanoid metabolites of DHA and n-3 DHA are members of the specialized proresolving mediator class of polyunsaturated fatty acid metabolites that possess potent anti-inflammation, tissue healing, and other activities (see specialized proresolving mediators).

Prominent docosanoids

Specialized proresolving mediator docosanoids

Potently bioactive agents of the specialized proresolving mediator class include:

  • DHA-derived Resolvins (Rv's) of the D series: RvD1, RvD2, RvD3, RvD4, RvD5, RvD6, AT-RvD1, AT-RvD2, AT-RvD3, AT-RvD4, AT-RvD5, and AT-RvD6 (see specialized proresolving mediators#DHA-derived Resolvins).
  • n-3 DPA-derived Rvs of the D series (RvD1n-3, RvD2n-3, and RvDD1n-3) and the T series (RvT1, TvT2, RvT3, and RvT4) (see specialized proresolving mediators#n-3 DPA-derived resolvins).
  • DHA-derived Neuroprotectins, also termed protectins: PD1, PDX, 17-epi PD1, and 10-epi-DHA1 (see specialized proresolving mediators#DHA-derived protectins/neuroprotectins).
  • n-3 DPA derived protectins: RD1n-3 and RvD1n-3 (see specialized proresolving mediators#n-3 DPA-derived resolvins)(see DPA-derived protectins/neuroprotectins.
  • DHA derived Maresins: MaR1, MaR2, 7-epi-Mar1, Mar-L1, and Mar-L2 (see specialized proresolving mediators#DHA-derived Maresins).
  • n-3 DPA-derived maresins: Mar1n-3, Mar2n-3, and Mar3n-3 (see specialized proresolving mediators#n-3 DPA-derived maresins).

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-docahexaenoicacid acid (17-HpDHA) and then rapidly reduce this hydroperoxide to 17S-hydroxy-4Z,7Z,10Z,13Z,15E,19Z-docahexaenoicacid acid (17-HDHA) and similarly metabolize DHA to 13S-hydroperoxy-4Z,7Z,10Z,14Z,16Z,19Z-docahexaenoicacid acid (13-HpDHA) and then to 13S-hydroxy-4Z,7Z,10Z,14Z,16Z,19Z-docahexaenoicacid 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] and dihomo-epoxyeicosatrienoic acids[12] and dihomo-EETs.[13]

References

Oily fish are a rich source of the DHA from which Docosanoids derive
  1. ↑ "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. 2015. doi:10.1016/j.bbalip.2014.08.010. PMID 25149823. 
  2. ↑ "Lipid mediators in the resolution of inflammation". Cold Spring Harbor Perspectives in Biology 7 (2): a016311. 2015. doi:10.1101/cshperspect.a016311. PMID 25359497. 
  3. ↑ "n-3 Fatty acid supplementation and proresolving mediators of inflammation". Current Opinion in Lipidology 27 (1): 26–32. 2016. doi:10.1097/MOL.0000000000000262. PMID 26655290. https://api.research-repository.uwa.edu.au/files/26432732/N_3_Fatty_acid_supplementation_and_prorresolving_mediators_of_inflammation._AAM_ID_11273143.docx. 
  4. ↑ "Dihydroxylated E,E,Z-docosatrienes. An overview of their synthesis and biological significance". Progress in Lipid Research 61: 1–18. 2016. doi:10.1016/j.plipres.2015.10.002. PMID 26545300. 
  5. ↑ "Measurement of products of docosahexaenoic acid peroxidation, neuroprostanes, and neurofurans". Lipidomics and Bioactive Lipids: Specialized Analytical Methods and Lipids in Disease. Methods in Enzymology. 433. 2007. pp. 127–43. doi:10.1016/S0076-6879(07)33007-3. ISBN 9780123739667. 
  6. ↑ "Current development in non-enzymatic lipid peroxidation products, isoprostanoids and isofuranoids, in novel biological samples". Free Radical Research 49 (7): 816–26. 2015. doi:10.3109/10715762.2014.960867. PMID 25184341. 
  7. ↑ "Omega-6 docosapentaenoic acid-derived resolvins and 17-hydroxydocosahexaenoic acid modulate macrophage function and alleviate experimental colitis". Inflammation Research 61 (9): 967–76. 2012. doi:10.1007/s00011-012-0489-8. PMID 22618200. 
  8. ↑ "15-lipoxygenase metabolites of docosahexaenoic acid inhibit prostate cancer cell proliferation and survival". PLOS ONE 7 (9): e45480. 2012. doi:10.1371/journal.pone.0045480. PMID 23029040. Bibcode: 2012PLoSO...745480O. 
  9. ↑ "The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution". Seminars in Immunology 27 (3): 200–15. 2015. doi:10.1016/j.smim.2015.03.004. PMID 25857211. 
  10. ↑ "Docosapentaenoic acid derived metabolites and mediators - The new world of lipid mediator medicine in a nutshell". European Journal of Pharmacology 785: 108–115. 2015. doi:10.1016/j.ejphar.2015.11.002. PMID 26546723. 
  11. ↑ "Synthesis of dihomoprostaglandins from adrenic acid (7,10,13,16-docosatetraenoic acid) by human endothelial cells". Biochim. Biophys. Acta 837 (1): 67–76. 1985. doi:10.1016/0005-2760(85)90086-4. PMID 3931686. 
  12. ↑ "Adrenic acid metabolites as endogenous endothelium-derived and zona glomerulosa-derived hyperpolarizing factors". Hypertension 55 (2): 547–54. 2010. doi:10.1161/HYPERTENSIONAHA.109.144147. PMID 20038752. 
  13. ↑ "Metabolism of adrenic acid to vasodilatory 1alpha,1beta-dihomo-epoxyeicosatrienoic acids by bovine coronary arteries.". Am J Physiol Heart Circ Physiol 292 (5): H2265–74. May 2007. doi:10.1152/ajpheart.00947.2006. PMID 17209008. 



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