Abstract

The present experiments were undertaken to examine in more detail differences in the oxidative metabolism of the two isomers of hexobarbital. The effects of inducing agents on the kinetics of hexobarbit, al metabolism were also studied. Studies on the in vitro time course of metabolism of the hexobarbital isomers in the rat, rabbit and mouse emphasize the early departure of enzyme activity from linearity. The metabolism of l-hexobarbital occurs for only five minutes whereas that of the d-isomer continues for much longer periods. Thus, the rapid departure from linearity of the metabolism of the racemic modification noted by many authors is probably due to the differing rates of metabolism of the two isomers. Pretreatment with either phenobarbital or 3-methylcholanthrene decrease the apparent K_m for the l-, but not the d-isomer, suggesting that the inducing agent brings about the synthesis of a qualitatively different microsomal hexobarbital oxidase system.