On the Fatty Acid and Hydrocarbon Hydroxylation in Rat Liver Microsomes

Abstract

The hydroxylation of heptane and laurate in rat liver microsomes has been studied with respect to catalytic components involved in the two reactions. The results have been compared with those obtained with aminopyrine and testosterone as substrates for microsomal hydroxylation. The hydroxylation of all four substrates was found to be inhibited by the oxidized form of cytochrome c and by carbon monoxide, as well as by NADP + in a competitive manner. Treatment of rats with phenobarbital in vivo resulted in a similar increase in the rate of hydroxylation of all four substrates as measured with the isolated liver microsomes. It is concluded that the hydroxylation of heptane and laurate as well as the oxidative demethylation of aminopyrine and hydroxylation of testosterone proceeds by way of a common microsomal hydroxylation enzyme system involving the NADPH‐cytochrome c reductase and the cytochrome P‐450. The broad action spectrum of this enzyme system is discussed, and the possibility is considered that fatty acids like laurate, in addition to certain steroid hormones, may serve as the physiological substrates for this enzyme system.