Reduction of beta-oxidation capacity of rat liver mitochondria by feeding orotic acid.
Rats were maintained on fat-free high carbohydrate diets either with or without orotic acid (1%, w/w), pantethine (1%, w/w), adenine (0.25%, w/w), and/or p-chlorophenoxyisobutyrate (0.25%, w/w). Oxidation of fatty acid by liver mitochondria was inhibited to less than half that of the control after administration of orotic acid. Activities of acyl-CoA dehydrogenases were markedly decreased by orotic acid administration, but the following enzyme activities were not, or only slightly decreased: acyl-CoA synthetase, carnitine acyltransferases, enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase and 3-ketoacyl-CoA thiolase. Simultaneous addition of pantethine in the orotic acid-containing diet prevented induction of fatty liver. It also prevented decreases in fatty acid oxidation capacity and acyl-CoA dehydrogenase activity. Introduction of adenine or p-chlorophenoxyisobutyrate, which reverse orotic acid-induced fatty liver, reversed oxidation and acyl-CoA dehydrogenase activities to control levels. The oxidation capacity of the peroxisomal system remained unchanged after administration of orotic acid.
D044944:Acyl-CoA Dehydrogenases / Q000037:antagonists & inhibitors*; D000225:Adenine / Q000008:administration & dosage; D000818:Animals; D002995:Clofibric Acid / Q000008:administration & dosage; D004032:Diet; D005227:Fatty Acids / Q000378:metabolism*; D005234:Fatty Liver / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D009963:Orotic Acid / Q000008:administration & dosage*; D010084:Oxidation-Reduction; D010204:Pantetheine / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains
D005227:Fatty Acids; D010204:Pantetheine; D002995:Clofibric Acid; D009963:Orotic Acid; D044944:Acyl-CoA Dehydrogenases; D000225:Adenine