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.
Leukotriene B4 (LTB4) compounds are produced by both enzymatic and non-enzymatic processes. The products of enzymatic origin, via Leukotriene A4 (LTA4) hydrolase, are stereospecifically 12(R). Non-enzymatic hydrolysis products are 50:50 mixtures at C-12, but are almost exclusively trans at C-6. Thus, the non-enzymatic hydrolysis product of LTA4 is 6-trans-12-epi LTB4. 12-epi LTB4 is an isomer which would not be expected to occur in either non-enzymatic hydrolysis products, or in the enzymatic products of LTA4 hydrolase. Compared to LTB4, 12-epi LTB4 has significantly reduced activity for the LTB4 receptor on human neutrophils (IC50 of 7.5 mM), and on guinea pig lung membranes with a (Ki of 4.7 mM). 12-epi LTB4 is an weak agonist at both the recombinant human BLT1 and BLT2 receptors, requiring approximately 10 mM for full activation of the receptor.