Arachidonic acid and other polyunsaturated fatty acids (PUFAs) are oxidatively metabolized by cyclooxygenase, lipoxygenases, and cytochromes P450. The primary metabolites from these pathways are subject to a further cascade of transformations resulting in a rich spectrum of biological active products. Recent studies have identified three principal sources of structural diversity and, hence, new eicosanoids: (a) multiple cytochrome P450 isoenzymes; (b) secondary metabolic routes includes transformation by beta-, omega-, and keto-oxidases; reductases; conjugation to taurine, glutathione, glucuronic acid, and other small molecular weight compounds; and dual pathway or transcellular oxidation; and (c) unregulated free radical processes associated with aging and/or pathophysiology that generate isoeicosanoids. The many urgent questions concerning the structure, origin, regulation, quantitation, and disposition of these eicosanoids will be addressed by (a) the isolation and structure elucidation of new eicosanoids; (b) the creation of efficient synthetic methodology and its application in unambiguous total syntheses of novel eicosanoids; (c) the preparation of selective metabolism inhibitors and eicosanoid analogs with modified activity and/or stability; (d) the development of immunoassays and instrumental assays for the detection and quantitation of eicosanoids, receptors, etc.; and (e) elucidation of the P450 active site.
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