Formation of Cytochrome P450 Metabolites of Arachidonic Acid by Human Placenta

Abstract

Saturated and polyunsaturated fatty acids can be oxygenated by cytochrome P450. The P450 pathway of the arachidonic acid cascade has been etablished in many organs, tissues and cells e. g. the kidney, the cardiovascular system, the nervous system, the skin, the corneal epithelium and in the platelets (1). Arachidonic acid can be oxygenated by P450 in several ways. Epoxidations lead to the regio- and enantioselective formation of four epoxyeicosatrienoic acids (EET’s). These epoxides are enzymatically degraded by hydrolases to the corresponding vicinal dihydroxy compounds (DHET’s). In another important class of P450 reactions arachidonic acid is hydroxylated to various HETE’s. Up to now only few reports about the P450 pathway in intauterine tissues have been published. Only in one investigation (2) a HPLC-peak cochromatographing with 14,15-EET was further characterised by its enhancement after α-naphthoflavone-treatment and its inhibition by SKF525A.