Drug metabolism in peroxisomes: involvement of peroxisomal beta-oxidation system in the oxidative chain-shortening of xenobiotic acyl compounds.
There are two kinds of beta-oxidation systems of fatty acids in mitochondria and peroxisomes in animal liver cells. These beta-oxidation systems may play different physiological roles in the cell. Peroxisomal beta-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 beta-oxidation systems is mainly due to the difference of characteristics of enzymes participating in the beta-oxidation in both organella. We have studied the beta-oxidation of xenobiotic acyl compounds and found that the peroxisomal beta-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 beta-oxidation of phenylfatty acids (PFAs), oxidative chain shortening of N-(alpha-methylbenzyl)azelaamic acid (C(9)) as a specific substrate for the peroxisomal beta-oxidation system, application of C(9) which is a specific substrate for peroxisomal beta-oxidation system for diagnosis of peroxisome disorders and participation of peroxisomal beta-oxidation system in the metabolic activation of prodrugs, YNK-01, by peroxisomal beta-oxidation system.
Suga
Tetsuya
T
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan. ccd97630@nyc.odn.ne.jp