Epoxygenases are a set of membrane-bound, heme-containing cytochrome P450 (CYP450 or just CYP) enzymes that metabolize polyunsaturated fatty acids (PUFAs) to epoxide products that have a range of biological activities.[1]
The most thoroughly-studied substrate of the CYP epoxygenases is the PUFA arachidonic acid (AA). Eicosanoids are created from AA in three pathways:
Like the first two pathways, the third acts as a signaling pathway wherein the eicosatrienoic acid epoxide products work as secondary signals to activate their parent or nearby cells and thereby orchestrate functional responses. However, these enzymes are not limited to metabolizing AA to these particular eicosanoids. Rather, they act broadly across other PUFAs and produce a range of products that are structurally analogous to the eicosanoids but often with different bioactivity profiles. This is particularly true of the CYP epoxygenases.
While there are specific and well-characterized receptor proteins which metabolites from the first pathways are known to activate, no such receptors have been fully characterized for the epoxide metabolites. Furthermore, there are relatively few lipoxygenases and cyclooxygenases in the first and second pathways that form metabolites. There are a much larger number of metabolite-forming CYP epoxygenases, and they have important differences in mammalian animal models that make the research inapplicable to human biology. Thus, it has been difficult to define clear roles for the epoxygenase-epoxide pathways in human physiology and pathology.