Drug Metabolism in Peroxisomes: Involvement of Peroxisomal β-Oxidation System in the Oxidative Chain-shortening of Xenobiotic Acyl Compounds

Summary: There are two kinds of β -oxidation systems of fatty acids in mitochondria and peroxisomes in animal liver cells. These β -oxidation systems may play different physiological roles in the cell. Peroxisomal β -oxidation system has been demonstrated to participate in the catabolism of intarcellular acyl compounds such as very long chain fatty acids, long chain dicarboxylic acids and bile acid precursors in addition to fatty acids. The difference of functions between mitochondrial and peroxisomal β -oxidation systems is mainly due to the difference of characteristics of enzymes participating in the β -oxidation in both organella. We have studied the β -oxidation of xenobiotic acyl compounds and found that the peroxisomal β -oxidation is involved in the chain-shortening of acyl side chains of several compounds. In the present review, the author describes the comparison between peroxisomal and mitochondrial β -oxidation of phenylfatty acids (PFAs), oxidative chain shortening of N-(α-methylbenzyl)azelaamic acid (C 9 ) as a specific substrate for the peroxisomal β -oxidation system, application of C 9 which is a specific substrate for peroxisomal β -oxidation system for diagnosis of peroxisome disorders and participation of peroxisomal β -oxidation system in the metabolic activation of prodrugs, YNK-01, by peroxisomal β -oxidation system.