(±)5(6)-dihet

5(6)-DiHET is a racemic compound synthesized through the action of epoxide hydrolases on 5(6)-EET, encompassing both enantiomeric forms. It serves as a quantitative marker for 5(6)-EET, facilitating its measurement by utilizing the compound's conversion to 5(6)-δ-lactone in solution. Additionally, 5(6)-DiHET activates large-conductance calcium-activated potassium (KCa1.1/BK) channels in rat small coronary artery smooth muscle cells, supporting its biological significance in vascular regulation. It also acts as a substrate for sheep seminal vesicle COX, leading to the in vitro production of 5,6-dihydroxy prostaglandin E1 and F1α metabolites. Notably, its levels diminish in the plasma of rats subjected to a high-fat diet, indicating a potential role in the pathophysiology of hyperlipidemia.

5,6-DiHET lactone is a lactonized form of 5,6-EET and 5,6-DiHET. In solution, 5(6)-EET degrades into 5(6)-DiHET and 5(6)-δ-lactone, which can be converted to 5(6)-DiHET and quantified by GC-MS. 5,6-DiHET potently induces vasodilation of isolated canine coronary arterioles, with 41% and 100% inhibition occurring at 0.01 and 100 pM, respectively. It also induces vasodilation in isolated human microvessels and increases intracellular calcium levels in a dose-dependent manner, an effect that can be blocked by the nitric oxide scavenger [L-NAME].

Eicosapentaenoic acid 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. (±)5(6)-DiHETE lactone is a 1,5 cyclic ester derived from (±)5(6)-DiHETE. While its biological activity is unknown, the selective capacity of (±)5(6)-DiHETE to form this lactone can be utilized to specifically quantify (±)5(6)-DiHETE in biological samples.

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(6)-EET is a fully racemic version of the enantiomeric forms biosynthesized from arachidonic acid by cytochrome P450 enzymes. In solution, 5(6)-EET degrades into 5,6-DiHET and 5(6)-δ-lactone, which can be converted to 5(6)-DiHET and quantified by GC-MS. In neuroendocrine cells, such as the anterior pituitary and pancreatic islets, 5(6)-EET has been implicated in the mobilization of calcium and hormone secretion. 5(6)-EET is an inhibitor of T-type voltage-gated calcium channels (Cav3) that inhibits isoforms Cav3.1, Cav3.2 (IC50 = 0.54 μM), and Cav3.3 and decreases nifedipine-resistant phenylephrine-induced vasoconstriction in isolated mouse mesenteric arteries via Cav3.2 blockade when used at a concentration of 3 μM. In addition, it is a substrate of COX-1 and COX-2, as measured by oxygen consumption and product formation assays when used at a concentration of 50 μM. (±)5(6)-EET is provided as a mixture of the free acid and lactone.

(±)5(6)-DiHET lactone is a 1,5 cyclic ester derived from (±)5(6)-DiHET , which, in turn, is a potential derivative of epoxidation of arachidonic acid at the α-5 double bond. (±)4(5)-DiHDPA lactone is a derivative of docosahexaenoic acid that is analogous to (±)5(6)-DiHET lactone. It is the 1,4 cyclic ester derived from (±)4(5)-DiHDPA, which is produced by epoxidation of DHA at the α-4 double bond. Its biological activity is unknown.