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      Oxidation of polyunsaturated fatty acids to produce lipid mediators


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          The chemistry, biochemistry, pharmacology and molecular biology of oxylipins (defined as a family of oxygenated natural products that are formed from unsaturated fatty acids by pathways involving at least one step of dioxygen-dependent oxidation) are complex and occasionally contradictory subjects that continue to develop at an extraordinarily rapid rate. The term includes docosanoids (e.g. protectins, resolvins and maresins, or specialized pro-resolving mediators), eicosanoids and octadecanoids and plant oxylipins, which are derived from either the omega-6 ( n-6) or the omega-3 ( n-3) families of polyunsaturated fatty acids. For example, the term eicosanoid is used to embrace those biologically active lipid mediators that are derived from C 20 fatty acids, and include prostaglandins, thromboxanes, leukotrienes, hydroxyeicosatetraenoic acids and related oxygenated derivatives. The key enzymes for the production of prostanoids are prostaglandin endoperoxide H synthases (cyclo-oxygenases), while lipoxygenases and oxidases of the cytochrome P450 family produce numerous other metabolites. In plants, the lipoxygenase pathway from C 18 polyunsaturated fatty acids yields a variety of important products, especially the jasmonates, which have some comparable structural features and functions. Related oxylipins are produced by non-enzymic means (isoprostanes), while fatty acid esters of hydroxy fatty acids (FAHFA) are now being considered together with the oxylipins from a functional perspective. In all kingdoms of life, oxylipins usually act as lipid mediators through specific receptors, have short half-lives and have functions in innumerable biological contexts.

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          Phospholipase A2 enzymes: physical structure, biological function, disease implication, chemical inhibition, and therapeutic intervention.

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            Dietary (n-3) fatty acids and brain development.

            The (n-3) fatty acids are essential dietary nutrients, and one of their important roles is providing docosahexaenoic acid [22:6(n-3)] (DHA) for growth and function of nervous tissue. Reduced DHA is associated with impairments in cognitive and behavioral performance, effects which are particularly important during brain development. Recent studies suggest that DHA functions in neurogenesis, neurotransmission, and protection against oxidative stress. These functions relate to the roles of DHA within the hydrophobic core of neural membranes and effects of unesterified DHA. Reviewed here are some of the recent studies that have begun to elucidate the role of DHA in brain development and function. A better understanding of development and age-specific changes in DHA transfer and function in the developing brain may provide important insight into the role of DHA in developmental disorders in infants and children, as well as at other stages of the lifespan.
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              Specialized pro-resolving mediators: endogenous regulators of infection and inflammation

              Key Points The immune response comprises not only pro-inflammatory and anti-inflammatory pathways but also pro-resolution mechanisms that serve to balance the need of the host to target microbial pathogens while preventing excess inflammation and bystander tissue damage. Specialized pro-resolving mediators (SPMs) are enzymatically derived from essential fatty acids to serve as a novel class of immunoresolvents that limit acute responses and orchestrate the clearance of tissue pathogens, dying cells and debris from the battlefield of infectious inflammation. SPMs are composed of lipoxins, E-series and D-series resolvins, protectins and maresins. Individual members of the SPM family serve as agonists at cognate receptors to induce cell-type specific responses. Important regulatory roles for SPMs have been uncovered in host responses to several microorganisms, including bacterial, viral, fungal and parasitic pathogens. SPMs also promote the resolution of non-infectious inflammation and tissue injury. Defects in host SPM pathways contribute to the development of chronic inflammatory diseases. With the capacity to enhance host defence and modulate inflammation, SPMs represent a promising translational approach to enlist host resolution programmes for the treatment of infection and excess inflammation. Supplementary information The online version of this article (doi:10.1038/nri.2015.4) contains supplementary material, which is available to authorized users.

                Author and article information

                Essays Biochem
                Essays Biochem
                Essays in Biochemistry
                Portland Press Ltd.
                September 2020
                03 July 2020
                : 64
                : 3 , Lipid Mediators
                : 401-421
                [1 ]James Hutton Institute, Invergowrie, Dundee, Scotland DD2 5DA, U.K.
                [2 ]School of Biosciences, Cardiff University, Cardiff CF10 3AX, Wales, U.K.
                Author notes
                Correspondence: John L. Harwood ( harwood@ 123456cardiff.ac.uk )
                © 2020 The Author(s).

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY). Open access for this article was enabled by the participation of Cardiff University in an all-inclusive Read & Publish pilot with Portland Press and the Biochemical Society under a transformative agreement with JISC.

                Page count
                Pages: 21
                Molecular Bases of Health & Disease
                Review Articles

                fatty acid metabolism,lipid mediators,polyunsaturated fatty acids


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