Mitochondrial, but not peroxisomal, beta-oxidation of fatty acids is conserved in coenzyme A-deficient rat liver.
Hepatic coenzyme A (CoA) plays an important role in cellular lipid metabolism. Because mitochondria and peroxisomes represent the two major subcellular sites of lipid metabolism, the present study was designed to investigate the specific impact of hepatic CoA deficiency on peroxisomal as well as mitochondrial beta-oxidation of fatty acids. CoA deficiency (47% decrease in free CoA and 23% decrease in total CoA) was produced by maintaining weanling male Sprague-Dawley rats on a semipurified diet deficient in pantothenic acid (the precursor of CoA) for 5 weeks. Hepatic mitochondrial fatty acid oxidation of short-chain and long-chain fatty acids were not significantly different between control and CoA-deficient rats. Conversely, peroxisomal beta-oxidation was significantly diminished (38% inhibition) in livers of CoA-deficient rats compared to control animals. Peroxisomal beta-oxidation was restored to normal levels when hepatic CoA was replenished. It is postulated that since the role of hepatic mitochondrial beta-oxidation is energy production while peroxisomal beta-oxidation acts mainly as a detoxification system, the mitochondrial pathway of beta-oxidation is spared at the expense of the peroxisomal pathway when liver CoA plummets. The present study may offer an animal model to investigate mechanisms involved in peroxisomal diseases.
Youssef
J A
JA
Division of Pharmacology, University of Missouri-Kansas City 64108, USA.
Song
W O
WO
Badr
M Z
MZ
D000818:Animals; D003065:Coenzyme A / Q000172:deficiency / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism*; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008830:Microbodies / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D010205:Pantothenic Acid / Q000172:deficiency / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D005227:Fatty Acids; D010205:Pantothenic Acid; D003065:Coenzyme A