Regulation of fatty acid oxidation of the heart by MCD and ACC during contractile stimulation.
We tested the hypothesis that the level of malonyl-CoA, as well as the corresponding rate of total fatty acid oxidation of the heart, is regulated by the opposing actions of acetyl-CoA carboxylase (ACC) and malonyl-CoA decarboxylase (MCD). We used isolated working rat hearts perfused under physiological conditions. MCD in heart homogenates was measured specifically by (14)CO(2) production from [3-(14)C]malonyl-CoA, and ACC was measured specifically based on the portion of total carboxylase that is citrate sensitive. Increased heart work (1 microM epinephrine + 40% increase in afterload) elicited a 40% increase in total beta-oxidation of exogenous plus endogenous lipids, accompanied by a 33% decrease in malonyl-CoA. The basal activity and citrate sensitivity of ACC (reflecting its phosphorylation state) and citrate content were unchanged. AMP levels were also unchanged. MCD activity, when measured at a subsaturating concentration of malonyl-CoA (50 microM), was increased by 55%. We conclude that physiological increments in AMP during the work transition are insufficient to promote ACC phosphorylation by AMP-stimulated protein kinase. Rather, increased fatty acid oxidation results from increased malonyl-CoA degradation by MCD.
Goodwin
G W
GW
Division of Cardiology, Department of Internal Medicine, University of Texas-Houston Medical School, Houston, Texas 77030, USA. ggoodwin@heart.med.uth.tmc.edu
Taegtmeyer
H
H
D000103:Acetyl-CoA Carboxylase / Q000494:pharmacology*; D000818:Animals; D002262:Carboxy-Lyases / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008316:Malonyl Coenzyme A / Q000378:metabolism; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats
D005227:Fatty Acids; D008316:Malonyl Coenzyme A; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase; D000103:Acetyl-CoA Carboxylase; D004837:Epinephrine