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Compartmentation of dicarboxylic acid β-oxidation in rat liver: importance of peroxisomes in the metabolism of dicarboxylic acids

1989; Elsevier BV; Volume: 990; Issue: 1 Linguagem: Inglês

10.1016/s0304-4165(89)80007-8

1872-8006

Hisashi Suzuki, Junji Yamada, Takafumi Watanabe, Tetsuya Suga,

Diet and metabolism studies

Peroxisomal and mitochondrial β-oxidation of dicarboxylic acids (DCAs) were investigated and compared. When isolated hepatocytes were incubated with DCAs of various chain lengths, H2O2 was derived from peroxisomal β-oxidation, the rates of its generation being comparable to those seen with monocarboxylic acids (MCAs), whereas the rates of ketone body production, a measure of mitochondrial β-oxidation, were much lower than those with MCAs. Peroxisomal β-oxidation measured by cyanide-insensitive NAD reduction exhibited similar chain-length specificities for both dicarboxylyl-CoAs (DC-CoAs) and monocarboxylyl-CoAs (MC-CoAs), except that the activities for DC-CoAs with 10–16 carbon atoms were about half of those of the corresponding MC-CoAs. In contrast, mitochondrial β-oxidation measured by antimycin A-sensitive O2 consumption had no activity for DCAs. In the study with purified enzymes, the reactivities of mitochondrial carnitine palmitoyltransferase and acyl-CoA dehydrogenase for DC-CoAs were much lower than those for MC-CoAs, while the reactivity of peroxisomal acyl-CoA oxidase for DC-CoAs was comparable to that for the corresponding MC-CoAs. Accordingly, the properties of carnitine palmitoyltransferase and acyl-CoA dehydrogenase must be the rate-limiting factors for mitochondrial β-oxidation, with the result that DCAs might hardly be oxidized in mitochondria. Comparative study of β-oxidation capacities of peroxisomes and mitochondria in the liver showed that DC12-CoA was hardly subjected to mitochondrial β-oxidation, and that the β-oxidation of DCAs in rat liver, therefore, must be carried out exclusively in peroxisomes.