Cyanide-insensitive and clofibrate enhanced beta-oxidation of dodecanedioic acid in rat liver. An indication of peroxisomal beta-oxidation of N-dicarboxylic acids.
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.
D000818:Animals; D002994:Clofibrate / Q000494:pharmacology*; D003486:Cyanides / Q000494:pharmacology*; D003998:Dicarboxylic Acids / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008830:Microbodies / Q000378:metabolism*; D009940:Organoids / Q000378:metabolism*; D010084:Oxidation-Reduction; D011190:Potassium Cyanide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D003486:Cyanides; D003998:Dicarboxylic Acids; C036836:dodecanedioic acid; D002994:Clofibrate; D011190:Potassium Cyanide