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They are derived from unesterified arachidonic acid first by the action of a 12lipoxygenase, of which the spinal eLOX3 isoform is most important, followed by two divergent pathways to produce 12 S hydroperoxy-5 c ,8 c ,10 t ,14 c -eicosatetraenoic acid (12 S HPETE), which can either be reduced to the hydroxy compound (12 S -HETE) or can be acted upon by a hepoxilin synthase (isomerase) to cause isomerization of the hydroperoxide group to an epoxide