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.
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.
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.
The cytochrome P450 (CYP) superfamily of membrane-bound (typically endoplasmic reticulum-bound) enzymes contain a heme cofactor and therefore are hemoproteins.
The superfamily comprises more than 11,000 genes categorized into 1,000 families that are distributed broadly throughout bacteria, archaea, fungi, plants, animals, and even viruses.
Certain CYP epoxygenases attack these double bonds to form their respective eicosatrienoic acid epoxide regioisomers.
[3][7][8][9] CYP2C8 and CYP2C9 form particularly large amounts of superoxide anion (chemical formula O−2) during their metabolism of polyunsaturated fatty acids; this reactive oxygen species is toxic to cells and may be responsible for some of the activities ascribed to the epoxides made by the two CYPs.
Possibly because of metabolizing and thereby inactivating the prostaglandins and/or because forming the bioactive metabolite, 12-HHT acid, rather than EETs, CYP2S1 may act to inhibit the function of monocytes and thereby limit inflammation as well as other immune responses.
That is, they are toxic to leukocytes as well as many other cell types and when injected into rodents produce multiple organ failure and respiratory distress.
[17] Some studies suggest but have not proven that leukotoxin and isoleukotoxin, acting primarily if not exclusively through their respective dihydroxy counterparts, are responsible for or contribute to multiple organ failure, respiratory distress, and certain other cataclysmic diseases in humans.
[20][23] These epoxides are also found in the plasma of humans, and their levels greatly increase in subjects given an α-linolenic acid-rich diet.
Investigation into the impact of these variants on the bearers' health (i.e. phenotype) is an invaluable area of research which offers the opportunity to define the function of the epoxygenases and their polyunsaturated fatty acid (PUFA) metabolites in humans.