Malonyl CoA control of fatty acid oxidation in the newborn heart in response to increased fatty acid supply.
The concentration of fatty acids in the blood or perfusate is a major determinant of the extent of myocardial fatty acid oxidation. Increasing fatty acid supply in adult rat increases myocardial fatty acid oxidation. Plasma levels of fatty acids increase post-surgery in infants undergoing cardiac bypass operation to correct congenital heart defects. How a newborn heart responds to increased fatty acid supply remains to be determined. In this study, we examined whether the tissue levels of malonyl CoA decrease to relieve the inhibition on carnitine palmitoyltransferase (CPT) I when the myocardium is exposed to higher concentrations of long-chain fatty acids in newborn rabbit heart. We then tested the contribution of the enzymes that regulate tissue levels of malonyl CoA, acetyl CoA carboxylase (ACC), and malonyl CoA decarboxylase (MCD). Our results showed that increasing fatty acid supply from 0.4 mmol/L (physiological) to 1.2 mmol/L (pathological) resulted in an increase in cardiac fatty acid oxidation rates and this was accompanied by a decrease in tissue malonyl CoA levels. The decrease in malonyl CoA was not related to any alterations in total and phosphorylated acetyl CoA carboxylase protein or the activities of acetyl CoA carboxylase and malonyl CoA decarboxylase. Our results suggest that the regulatory role of malonyl CoA remained when the hearts were exposed to high levels of fatty acids.
Onay-Besikci
Arzu
A
Department of Pharmacology, Faculty of Pharmacy, Ankara University, Turkey. onay@pharmacy.ankara.edu.tr
Sambandam
Nandakumar
N
D055372:AMP-Activated Protein Kinases; D000105:Acetyl Coenzyme A / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002262:Carboxy-Lyases / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002952:Citric Acid Cycle; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000378:metabolism* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011817:Rabbits
D009097:Multienzyme Complexes; D019308:Palmitic Acid; D008316:Malonyl Coenzyme A; D000105:Acetyl Coenzyme A; D002334:Carnitine O-Palmitoyltransferase; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase; D000103:Acetyl-CoA Carboxylase; D005947:Glucose