AENDO October 40/4

Goodwin, Gary W., and Heinrich Taegtmeyer. Regulation of fatty acid oxidation of the heart by MCD and ACC during contractile stimulation. Am. J. Physiol. 277 (Endocrinol. Metab. 40): E772–E777, 1999.—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 CO2 production from [3-14C]malonyl-CoA, and ACC was measured specifically based on the portion of total carboxylase that is citrate sensitive. Increased heart work (1 μM epinephrine 1 40% increase in afterload) elicited a 40% increase in total b-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 μM), 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.