Selective inhibition of hepatic peroxisomal fatty acid β-oxidation by enoximone

Abstract

Although β-oxidation of fatty acids occurs in both peroxisomes and mitochondria, β-oxidizing enzymes in these organelles have distinct differences in their specifity and sensitivity to inhibitors. In this study, the effects of the phosphodiesterase inhibitor enoximone on hepatic peroxisomal and mitochondrial β-oxidation were investigated. In liver homogenates from control rats, cyanide-insensitive peroxisomal β-oxidation of palmitoyl-CoA was inhibited progressively by increasing concentrations of enoximone. Similar results were obtained in liver homogenates from rats pretreated with the known peroxisomal proliferator diethylhexylphthalate. In contrast, mitochondrial β-oxidation of palmitoyl-CoA was not inhibited by enoximone. These data show that enoximone selectively inhibits basal as well as induced peroxisomal, but not mitochondrial, β-oxidation of the CoA thioester of long-chain fatty acids. The availability of specific inhibitors of peroxisomal β-oxidation should prove useful in elucidating regulatory mechanisms operative in this pathway in normal as well as in proliferated peroxisomes.