Cyanide-insensitive and clofibrate enhanced beta-oxidation of dodecanedioic acid in rat liver. An indication of peroxisomal beta-oxidation of N-dicarboxylic acids

Abstract

The beta-oxidation rate of dodecanedioic acid in rat liver homogenates (600 X g supernatant fraction) was determined by simultaneous measurements of the C6-C12-dicarboxylic acids, i.e., adipic, suberic, sebacic and dodecanedioic acids, in relation to time in assays incubated with dodecanedioic acid. Measurements were performed by a combined gas chromatographic-mass spectrometric technique, i.e., selected ion-monitoring. The beta-oxidation rate was registered as the consumption rate of dodecanedioic acid and as the initial rise in the concentrations of C6-C10-dicarboxylic acids. The beta-oxidation rate of C8-C12-dicarboxylic acids was increased many times in homogenates from clofibrate-treated rats. Moreover, it was unexpectedly found that 2.0 mM cyanide was unable to inhibit the beta-oxidation rate of the dicarboxylic acids in vitro, but in fact caused a minor increase in the rate of beta-oxidation in homogenates from both normal and clofibrate-treated rats. It was concluded that the present results strongly indicate the existence of a peroxisomal beta-oxidation of dicarboxylic acids.