Cleavage of 3-phenoxybenzoic acid by chicken microsomal preparations

3-Phenoxybenzoic acid, labelled at either the 3-phenoxy[U-ring C-14] or carbonyl C-14, produced the corresponding labelled transitory metabolite 4'-hydroxy-3-phenoxybenzoic acid when incubated with chicken liver microsomal preparation. The other radioactive reaction product identified from the metabolism of the carbonyl-labelled 3-phenoxybenzoic acid was labelled 3-hydroxybenzoic acid, whereas metabolism of the [U-ring] labelled 3-phenoxybenzoic acid produced labelled hydroquinone in addition to 4'-hydroxy-3-phenoxybenzoic acid. Formation of both 4'-hydroxy-3-phenoxybenzoic acid, and its subsequent conversion to 3-hydroxybenzoic andhydroquinone were NADPH and oxygen dependent. The reaction was inhibited by carbon monoxide, but not by piperonyl butoxide or metyrapone. The inhibition by carbon monoxide suggests that the enzyme(s) involved in the cleavage is a form of P450. The enzyme(s) is a monooxygenase and has requirement for NADPH and oxygen.