(±)11,12-DiHETE is a dihydroxy metabolite of EPA produced by cytochrome P450-mediated epoxide formation and subsequent hydrolysis by epoxide hydrolase. Plasma levels of (±)11,12-DiHETE are increased over baseline after an oral dose of 1008 mg EPA.

(±)8,9-DiHETE is a major metabolite of the 20:5 ω-3 fatty acid eicosapentaenoic acid .[1] It is produced in rat liver microsomes, but not renal microsomes, by the generation of the unstable intermediate 8,9-epoxy eicosatetraenoic acid from EPA by cytochrome P450 monooxygenases. Dietary EPA supplementation in humans results in substantial urinary excretion of vicinal diols, including 8,9, 11,12, and 14,15 forms.[2]

5(S),6(R)-DiHETE is a dihydroxy polyunsaturated fatty acid and a nonenzymatic hydrolysis product of leukotriene A4 (LTA4). Mouse liver cytosolic epoxide hydrolase catalyzes the conversion of LTA4 to 5(S),6(R)-DiHETE. It is a weak LTD4 receptor agonist in guinea pig lung membranes. It induces guinea pig ileum contraction with an ED50 value of 1.3 μM.

5(S),12(S)-DiHETE is a natural bioactive lipid derived from arachidonic acid . It is synthesized by glycogen-induced rabbit peritoneal polymorphonuclear leukocytes (PMNLs) incubated with AA. 5(S),12(S)-DiHETE can be produced by successive oxygenation of AA by 5-lipoxygenase (5-LO) in platelets and 12-LO in leukocytes. It can also be synthesized from 12(S)-HETE by 5-LO, in the presence of 5-LO activating protein (FLAP), activated with calcium ionophore. 5(S),12(S)-DiHETE is an epimer of leukotriene B4 that is weakly chemotactic for PMNL.

Eicosapentaenoic acid is an ω-3 fatty acid abundantly available in marine organisms. (±)17(18)-DiHETE is one of the major metabolites produced when eicosapentaenoic acid (EPA) is incubated with various rat tissue homogenates or cynomolgus monkey seminal vesicles. The route of production of (±)17(18)-DiHETE likely proceeds through cytochrome P450-catalyzed epoxidation at the ω-3 double bond followed by conversion to the vicinal diols by epoxide hydrolase. EPA is also metabolized preferentially by Gaeumannomyces graminis to (±)17(18)-DiHETE.

5(S),6(S)-DiHETE is one of the four diastereomeric 5,6-dihydroxy acids produced from the non-enzymatic hydrolysis of LTA4. 5(S),6(S)-DiHETE does not have significant leukotriene-like activity.

8(S),15(S)-DiHETE is formed when 15(S)-HETE is subjected to further oxidation by 15-LO. It causes eosinophil chemotaxis with an ED50 value of 1.5 μM but is not chemotactic for neutrophils. 8(S),15(S)-DiHETE antagonizes the hyperalgesic activity of 8(R),15(S)-DiHETE and LTB4 in the rat hind paw pain model.

5(S),6(R)-11-trans DiHETE is a C-11 double bond isomer of 5(S),6(R)-DiHETE that is formed by the enzymatic isomerization of 5(S),6(R)-DiHETE by a membrane bound factor. 5(S),6(R)-11-trans DiHETE has been found in rat kidney homogenates and is potentially formed by the epoxide hydrolase pathway in this tissue. The isomerase activity responsible for the conversion of leukotriene B4 (LTB4) to 6-trans LTB4 in rat kidney homogenates has also been implicated in its formation. 5(S),6(R)-11-trans DiHETE is not a substrate for soybean lipoxygenase. The biological activity of 5(S),6(R)-11-trans DiHETE has not been reported.

Eicosapentaenoic acid is an ω-3 polyunsaturated fatty acid that is abundant in marine organisms and fish oils. EPA is metabolized, in part, through cytochrome P450-catalyzed epoxidation followed by conversion to the vicinal diols by epoxide hydrolases. (±)5(6)-DiHETE is a possible metabolite produced from EPA following epoxidation of the α-5 double bond. The biological activity of (±)5(6)-DiHETE has not been documented.

5(S),15(S)-DiHETE is synthesized by 15-LO from 5(S)-HETE. It potentiates the degranulation of human PMNL in response to PAF, but not fMLP, calcium ionophore A23187, or LTB4. 5(S),15(S)-DiHETE is chemotactic for eosinophils with an ED50 value of 0.3 μM.