Compartmentation of dicarboxylic acid beta-oxidation in rat liver: importance of peroxisomes in the metabolism of dicarboxylic acids.
Peroxisomal and mitochondrial beta-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 beta-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 beta-oxidation, were much lower than those with MCAs. Peroxisomal beta-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 beta-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 beta-oxidation, with the result that DCAs might hardly be oxidized in mitochondria. Comparative study of beta-oxidation capacities of peroxisomes and mitochondria in the liver showed that DC12-CoA was hardly subjected to mitochondrial beta-oxidation, and that the beta-oxidation of DCAs in rat liver, therefore, must be carried out exclusively in peroxisomes.
Suzuki
H
H
Department of Clinical Biochemistry, Tokyo College of Pharmacy, Japan.
Yamada
J
J
Watanabe
T
T
Suga
T
T
D044944:Acyl-CoA Dehydrogenases / Q000378:metabolism; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D002333:Carnitine Acyltransferases / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D003065:Coenzyme A / Q000378:metabolism; D003998:Dicarboxylic Acids / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000648:ultrastructure*; D008297:Male; D008830:Microbodies / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
D003998:Dicarboxylic Acids; D007657:Ketone Bodies; D009243:NAD; D000968:Antimycin A; D006861:Hydrogen Peroxide; D044944:Acyl-CoA Dehydrogenases; D002333:Carnitine Acyltransferases; D002334:Carnitine O-Palmitoyltransferase; D003065:Coenzyme A