4.6 Review

Polyunsaturated fatty acids and fatty acid-derived lipid mediators: Recent advances in the understanding of their biosynthesis, structures, and functions

Journal

PROGRESS IN LIPID RESEARCH
Volume 86, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.plipres.2022.101165

Keywords

Elovanoids; FAHFA; Fatty acid desaturase; Lipid mediators; Maresins; Omega-3 PUFA; Oxylipins; Protectins; Resolvins; SPM

Funding

  1. Eunice Kennedy Shriver National Institute of Child Health and Human Development [R21-HD095391-01A1]
  2. USDA National Institute of Food and Agriculture, Hatch/Taha [1008787]
  3. National Institutes of Health USA [R35GM139430, R01GM38765]
  4. European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme [677542]
  5. Barts Charity a Sir Henry Dale Fellowship - Wellcome Trust [MGU0343]
  6. Barts Charity a Sir Henry Dale Fellowship - Royal Society [107613/Z/15/Z]
  7. National Eye Institute [R01 EY005121]
  8. National Institute of Neurological Disorders and Stroke [R01 NS109221, R01 NS104117]
  9. EENT Foundation of New Orleans
  10. NIFA [1008787, 912972] Funding Source: Federal RePORTER

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Polyunsaturated fatty acids are important components of cell membranes and play a role in cellular function. They can also serve as precursors for lipid mediators called oxylipins. Oxylipins are formed through enzymatic or non-enzymatic pathways and include eicosanoids and other lipid mediators. This review summarizes current knowledge about the structure and functions of nonclassical oxylipins.
Polyunsaturated fatty acids (PUFAs) are structural components of membrane phospholipids, and influence cellular function via effects on membrane properties, and also by acting as a precursor pool for lipid mediators. These lipid mediators are formed via activation of pathways involving at least one step of dioxygen-dependent oxidation, and are consequently called oxylipins. Their biosynthesis can be either enzymatically-dependent, utilising the promiscuous cyclooxygenase, lipoxygenase, or cytochrome P450 mixed function oxidase pathways, or nonenzymatic via free radical-catalyzed pathways. The oxylipins include the classical eicosanoids, comprising prostaglandins, thromboxanes, and leukotrienes, and also more recently identified lipid mediators. With the advent of new technologies there is growing interest in identifying these different lipid mediators and characterising their roles in health and disease. This review brings together contributions from some of those at the forefront of research into lipid mediators, who provide brief introductions and summaries of current understanding of the structure and functions of the main classes of nonclassical oxylipins. The topics covered include omega-3 and omega-6 PUFA biosynthesis pathways, focusing on the roles of the different fatty acid desaturase enzymes, oxidized linoleic acid metabolites, omega-3 PUFA-derived specialized pro-resolving mediators, elovanoids, nonenzymatically oxidized PUFAs, and fatty acid esters of hydroxy fatty acids.

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