Diphenyl ether cleavage of 3-phenoxybenzoic acid by chicken kidney microsomal preparations

Incubation of 3-phenoxybenzoic acid[carbonyl-14C] with chicken kidney microsomal fraction produced two major radioactive compounds identified as 3-hydroxybenzoic acid and 4'-hydroxy-3-phenoxybenzoic acid. It was found that 4'-hydroxy-3-phenoxybenzoic acid was transitory in nature and was rapidly converted into 3-hydroxybenzoic acid. The conversion of 3-phenoxybenzoic acid to the products was NADPH dependent. This is a first example of metabolism of 4'-hydroxy-3-phenoxybenzoic acid to 3-hydroxybenzoic acid. Cytosol did not promote any cleavage. Similar activities were present in liver microsomes, but the activity was lower than in kidney. Intestinal contents, homogenates, or microsomal fractions did not metabolize 3-phenoxybenzoic acid.