a variety of hepoxilin isomers and occur as an artifact of tissue processing. Finally, cellular peroxidases readily and rapidly reduce 12(S)-HpETE to its hydroxyl analog, 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12S-HETE; see 12-hydroxyeicosatetraenoic acid; this reaction competes with the hepoxilin-forming reaction and in cells expressing very high peroxidase activity may be responsible for blocking the formation of the hepoxilins. ALOX15 is responsible for metabolizing arachidonic acid to 14,15-HxA3 and 14,15-HxB3 as indicated in the following two-step reaction which first forms 15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (15S-HpETE) and then two specific isomers of 11S/R-hydroxy-14S,15S-epoxy-5Z,8Z,12E-eicosatrienoic acid (i.e. 14,15-HxA3) and 13S/R)-hydroxy-14S,15S-epoxy-5Z,8Z,11Z-eicosatrienoic acid (i.e. 14,15-HxB3): ALOX15 appears capable of conducting both steps in this reaction although further studies may show that ALOXE3, non-enzymatic rearrangements, and the reduction of 15S-HpETE to 15(S)-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (i.e. 15S-HETE; see 15-hydroxyicosatetraenoic acid) may be involved in the production of 14,15-HxA3 and 14,15-HxB3 as they are in that of HxA3 and HxB3. Production of the hepoxilin-like metabolites of docosahexaenoic acid, 7R/S-hydroxy-10,11-epoxy-4Z,7E,13Z,16Z,19Z-docosapentaenoic acid (i.e. 7-hydroxy-bis-α-dihomo-HxA5) and 10-hydroxy-13,14-epoxy-4Z,7EZ,11E,16Z,19Z-docosapentaenoic acid (i.e. 10-hydroxy-bis-α-dihomo-HxA5) was formed (or inferred to be formed based on the formation of their tihydroxy metabolites (see trioxilins, below) as a result of adding docosahexaenoic acid to the pineal gland or hippocampus isolated from rats; the pathway(s) making these products has not been described. A hepoxilin-like metabolite of linoleic acid forms in the skin of humans and rodents. This hepoxilin is esterified to sphinganine in a lipid complex termed EOS (i.e. esterified omega-hydroxyacyl-sphingosine, see Lipoxygenase#Biological function and classification#Human lipoxygenases) that also contains a very long chain fatty acid. In this pathway, ALOX12B metabolizes the esterified linoleic acid to its 9R-hydroperoxy derivative and then ALOXE3 metabolizes this intermediate to its 13R-hydroxy-9R,10R-epoxy product. The pathway functions to deliver very long chain fatty acids to the cornified lipid envelope of the skin surface. Further metabolism HxA3 is extremely unstable and HxB3 is moderately unstable, rapidly decomposing to their tri-hydroxy products, for example, during isolation procedures that use an even mildly acidic methods; they are also rapidly metabolized enzymatically in cells to these same tri-hydroxy products, termed trioxilins (TrX's) or trihydroxyeicoxatrienoic acids (THETA's); HxA3 is converted to 8,11,12-trihydroxy-5Z,9E,14Z-eicosatrienoic acid (trioxilin A3 or TrXA3) while TxB3 is converted to 10,11,12-trihydroxy-5Z,8Z,14Z-eicosatrienoic acid (trioxilin B3 or TrXB3). A third trihydroxy acid, 8,9,12-trihydroxy-5Z,10E,14Z eicosatrienoic acid (trioxilin C3 or TrXC3), has been detected in rabbit and mouse aorta tissue incubated with arachidonic acid. The metabolism of HxA3 to TrXA3 and HXB3 to TrX is accomplished by soluble