Arachidonic acid is converted by microsomal CYP450 enzymes to a variety of epoxides, ω-1 and ω-hydroxylated compounds via what is known as the epoxidase pathway.[1],[2],[3] MS-PPOH is a selective inhibitor of the epoxygenation reactions catalyzed by specific CYP450 isozymes.[4]. MS-PPOH inhibits the formation of arachidonate 11,12-epoxides by CYP4A2 and CYP4A3 enzymes with an IC50 value of 13 µM, but has no effect on the formation of 20-HETE, the ω-hydroxylation product of CYP4A1.[5]
Reference:
[1]. Capdevila, J.H., Karara, A., Waxman, D.J., et al. Cytochrome P-450 enzyme-specific control of the regio- and enantiofacial selectivity of the microsomal arachidonic acid epoxygenase The Journal of Biological Chemisty 265, 10865-10871 (1990).
[2]. Sacerdoti, D., Abraham, N.G., McGiff, J.C., et al. Renal cytochrome P-450-dependent metabolism of arachidonic acid in spontaneously hypertensive rats Biochemical Pharmacology 37, 521-527 (1988).
[3]. Fitzpatrick, F.A., and Murphy, R.C. Cytochrome P-450 metabolism of arachidonic acid: Formation and biological actions of “epoxygenase”-derived eicosanoids Pharmacol. Rev. 40(4), 229-241 (1989).
[4]. Imig, J.D., Falck, J.R., and Inscho, E.W. Contribution of cytochrome P450 epoxygenase and hydroxylase pathways to afferent arteriolar autoregulatory responsiveness British Journal of Pharmacology 127, 1399-1405 (1999).
[5]. Wang, M.H., Brand-Schieber, E., Zand, B.A., et al. Cytochrome P450-derived arachidonic acid metabolism in the rat kidney: Characterization of selective inhibitors Journal of Pharmacology and Experimental Therapeutics 284(3), 966-973 (1998).