Oxidation of polyunsaturated fatty acids to produce lipid mediators

Abstract

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 C20 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 C18 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.

Keywords: fatty acid metabolism; lipid mediators; polyunsaturated fatty acids.

Figure 1. Generation of the classic eicosanoids (taken from [2] with permission)

Figure 2. Cyclooxygenase activity (taken from [2] with permission)

Figure 3. Prostaglandin precursors and products

Figure 4. Conversion of cyclooxygenase endoperoxide products to different types of eicosanoids (adapted and re-drawn from [2])

Figure 5. Leukotriene biosynthesis

Figure 6. Examples of lipoxin biosynthesis

Figure 7. Metabolism of arachidonic acid by the cytochrome P450 epoxygenase pathway (taken from [2] with permission)

Figure 8. Action of CYP450 oxidases on EPA and DHA (taken from [2] with permission)

Figure 9. Examples of specialised pro-resolving mediators (SPMs)

Figure 10. Biosynthesis of SPMs

Figure 11. Biosynthesis of protectin D1

Figure 12. Biosynthesis of E-series resolvins

Figure 13. Aspirin-triggered resolvins

Figure 14. Biosynthesis of maresins

Figure 15. Conversion of the essential fatty acids to 20- or 22-carbon PUFAs (re-drawn from [90] with permission)