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Division of Cardiology, Department of Internal Medicine, University of Texas-Houston Medical School, Houston, Texas 77030
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
14CO2
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 + 40% increase in afterload) elicited a 40% increase in
total 
-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.
malonyl-CoA; citrate; acetyl-CoA carboxylase; malonyl-CoA decarboxylase
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