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Chunk #5 — Tight regulation of epoxygenated fatty acids (EFAs) — EFA production

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Soluble epoxide hydrolase inhibition, epoxygenated fatty acids and nociception.
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the last to be discovered in the early 1980s. Thus less is known about these molecules. While the cytochrome P450 family of enzymes is often associated with xenobiotic metabolism, their endogenous roles include steroid metabolism and EETs formation. More recently, it became clear that epoxy fatty acids from a number of PUFAs are generated by cytochrome P450s. Epoxygenation of these endogenous PUFAs such as linoleic, linolenic, AA, DHA and eicosapentaenoic acid (EPA) lead to multiple regioisomers of epoxygenated metabolites of the parent lipids [15, 16]. While each PUFA can be metabolized to a number of different monoepoxy fatty acid regioisomers, each of the regioisomers also have two possible geometric isomers (cis or trans) and two possible enantiomers for each geometric isomer, thus comprising a large number of biological active lipid metabolites [17, 18]. Most natural PUFAs are in Z or cis isomers which yield cis epoxides. It was not clear until recently if this molecular diversity was paralleled in functional diversity. However the large number of biological processes that the EFAs mediate support the idea that different EFAs have non-overlapping functions [19–22]. With the exception of the epoxides of LA, the plasma and cellular levels of free EFAs are typically