Peroxisomal and mitochondrial beta-oxidation of monocarboxylyl-CoA, omega-hydroxymonocarboxylyl-CoA and dicarboxylyl-CoA esters in tissues from untreated and clofibrate-treated rats.
In control rats, long-chain monocarboxylyl-CoA, omega-hydroxymonocarboxylyl-CoA, and dicarboxylyl-CoA esters were substrates for hepatic, renal, and myocardial peroxisomal beta-oxidation. The latter enzyme system could not be detected in skeletal muscle. Clofibrate treatment resulted in an enhancement of peroxisomal beta-oxidizing capacity in various tissues. Intact mitochondria from control rat liver and kidney cortex incubated in the presence of L-carnitine were capable of oxidizing long-chain monocarboxylyl-CoAs and omega-hydroxymonocarboxylyl-CoAs but not dicarboxylyl-CoAs. However, control rat liver mitochondria permeabilized by digitonin oxidized dodecanedioyl-CoA indicating that the liver mitochondrial beta-oxidation system can act on dicarboxylyl-CoA esters even if the overall intact mitochondrial system is inactive on these substrates. Intact liver mitochondria from clofibrate-treated animals rapidly oxidized lauroyl-CoA and 12-hydroxylauroyl-CoA but not dodecanedioyl-CoA. These mitochondria were active on hexadecanedioyl-CoA and this activity amounted to 20-25% of that measured with palmitoyl-CoA and 16-hydroxypalmitoyl-CoA as substrates. No mitochondrial dicarboxylyl-CoA oxidation could be detected in kidney cortex from animals receiving clofibrate in their diet. Heart and skeletal muscle intact mitochondria from untreated and clofibrate-treated rats were capable of oxidizing each type of acyl-CoA as a substrate. Dicarboxylyl-CoA synthetase and carnitine dicarboxylyltransferase activities were detected in various tissues from untreated and clofibrate-treated rats with the exception of carnitine dodecanedioyltransferase reaction in livers from untreated and clofibrate-treated rats. In skeletal muscle, the acyl-CoA synthetase activities could be detected only in the presence of detergents.
Vamecq
J
J
Laboratoire de Chimie Physiologique, International Institute of Cellular and Molecular Pathology, Brussels, Belgium.
Draye
J P
JP
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D002333:Carnitine Acyltransferases / Q000378:metabolism; D002994:Clofibrate / Q000494:pharmacology*; D003066:Coenzyme A Ligases / Q000378:metabolism; D003998:Dicarboxylic Acids / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008830:Microbodies / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000201:enzymology; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D000214:Acyl Coenzyme A; D003998:Dicarboxylic Acids; D005227:Fatty Acids; D002333:Carnitine Acyltransferases; D003066:Coenzyme A Ligases; C047027:dicarboxylic acid-CoA synthetase; D002994:Clofibrate