The Enzymic Formation of a Methylenedioxyphenyl Derivative Exhibiting an Isocyanide-like Spectrum with Reduced Cytochrome P-450 in Hepatic Microsomes

Abstract

1. Methylenedioxyphenyl compounds (piperonyl butoxide, methylene-dioxybenzene, isosafrole) were metabolized by rat liver microsomes in the presence of oxygen and NADPH (but not NADH) to give products which exhibited an isocyanide-like absorption spectrum with reduced cytochrome P-450 of liver microsomes.

2. The presence of hexobarbital inhibited the formation of the isocyanide-like spectrum, presumably by inhibiting the formation of the metabolite.

3. The optical spectrum absorption characteristics of the complex of the metabolite with reduced cytochrome P-450 varied with changes in pH.

4. The metabolite, or the metabolite-cytochrome P-450 complex formed, was sufficiently stable to survive the oxidation and re-reduction of the microsomal cytochrome P-450.