The aromatization of hydrogenated derivatives of benzoic acid in animal tissues

Abstract

The conversion of cyclohexanecarboxylic acid to benzoic acid, with urinary excretion of hippuric acid, was studied in the intact rabbit which was found unable to aromatize appreciably any of the 7 possible monohydroxy derivatives of cyclohexanecarboxylic acid (except trans-4-hydroxycyclohexanecarboxylic acid which was feebly (10%) aromatized). The [DELTA]1 - and [DELTA]3-cyclohexenecarboxylic acids were aromatized about as well as cyclohexanecarboxylic acid, the [DELTA]2-acid somewhat less well. The reaction was in excised tissues by means of tissue slices, homogenates and extracts under various conditions of incubation. The liver was most active of the rabbit tissue slices examined in aromatization and the kidney next. Hippuric acid was isolated from rabbit liver slices incubated with cyclohexanecarboxylic acid. Appreciable quantities of benzoic acid were not formed by the rabbit liver slices from any of the monohydroxycyclohexanecarboxylic acids. They aromatized [DELTA]3-cyclohexenecarboxylic acid more readily than cyclohexanecarboxylic acid, the [DELTA]1 compound much less rapidly and the [DELTA]2 compound at an intermediate rate. The [DELTA]3-cyclohexenecarboxylic acid was the only one of the 3 un-saturated compounds aromatized at a sufficient rate both in the whole animal and in liver slices for it to be a possible intermediate in cyclohexanecarboxylic acid oxidation. Homogenates of rat liver which vigorously oxidize fatty acids do not aromatize appreciably cyclohexanecarboxylic acid or any of its monohydroxy or mono-unsaturated derivatives. Only the cis-4-hydroxy derivative was vigorously oxidized. Most of the other hydroxy compounds depressed the O2 uptake. Cyclo-hexanecarboxylic acid and its [DELTA]3 derivative (0.003 [image]) depressed the oxidation of octanoate by rat liver homogenate. Rabbit liver homogenates behaved similarly. Fatty acid dehydrogenase prepns. from liver tissue were unable to dehydrogenate cyclohexanecarboxylic acid. Quinic acid (1,3,4,5-tetrahydroxy-cyclohexanecarboxylic acid) was converted to hippuric acid in good yield by man, but not by other species tested.