Acylcarnitine formation and fatty acid oxidation in hepatocytes from rats treated with tetradecylthioacetic acid (a 3-thia fatty acid).
In livers of rats fed a single morning dose of 100 mg tetradecylthioacetic acid (TTA) total long-chain acyl-CoA increased significantly to 3 times control levels within 6 h, then the level declined almost to control value within the next morning. Hepatic malonyl-CoA was reduced 75% 6 h after TTA treatment. From 6 to 24 h malonyl-CoA increased about 10-fold to about 3 times that of controls. Paradoxically there was nearly a 2-fold higher oxidation of both [1-14C]palmitic acid (0.5 mM) and [1-14C]oleic acid (0.5 mM) in hepatocytes isolated from rats 24 h after TTA treatment compared to controls. After 6 h, when malonyl-CoA was at a minimum in vivo, fatty acid oxidation in cells was not increased. Acylcarnitine formation in digitonin permeabilized hepatocytes isolated 24 h after administration of TTA was increased both in the absence and in the presence of malonyl-CoA. At 24 h peroxisomal palmitoyl-CoA oxidase activity was not increased. The results suggest that an increased CPT activity and increased acylcarnitine formation in the presence of malonyl-CoA is a delayed response to increased acyl-CoA levels. Furthermore, in hepatocytes isolated after 24 h incorporation of [1-14C]oleic acid into triacylglycerols was significantly reduced. The data show that in hepatocytes isolated from rats 24 h after administration of a single dose of TTA, there is a diversion of hepatic acyl-CoA from synthesis of triacylglycerols into beta-oxidation in the mitochondria.
Skrede
S
S
Institute of Medical Biochemistry, University of Oslo, Norway.
Bremer
J
J
D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008316:Malonyl Coenzyme A / Q000032:analysis; D008930:Mitochondria, Liver / Q000187:drug effects; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D010743:Phospholipids / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000494:pharmacology*; D014280:Triglycerides / Q000096:biosynthesis
D000214:Acyl Coenzyme A; D005227:Fatty Acids; D009829:Oleic Acids; D010169:Palmitic Acids; D010743:Phospholipids; D013440:Sulfides; D014280:Triglycerides; D019301:Oleic Acid; D019308:Palmitic Acid; D008316:Malonyl Coenzyme A; C062078:1-(carboxymethylthio)tetradecane; D002334:Carnitine O-Palmitoyltransferase