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In pressure overload-induced hypertrophy, the heart increases its reliance on glucose as a fuel while decreasing fatty acid oxidation. A key regulator of this substrate switching in the hypertrophied heart is peroxisome proliferator-activated receptor alpha (PPARalpha). We tested the hypothesis that down-regulation of PPARalpha is an essential component of(More)
We determined the contribution of all major energy substrates (glucose, glycogen, lactate, oleate, and triglycerides) during an acute increase in heart work (1 microM epinephrine, afterload increased by 40%) and the involvement of key regulatory enzymes, using isolated working rat hearts exhibiting physiologic values for contractile performance and oxygen(More)
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(More)
A protein geranylgeranyltransferase (PGT) that catalyzes the transfer of a 20-carbon prenyl group from geranylgeranyl pyrophosphate to a cysteine residue in protein and peptide acceptors was detected in bovine brain cytosol and partially purified. The enzyme was shown to be distinct from a previously characterized protein farnesyltransferase (PFT). The PGT(More)
BACKGROUND The glucose tracer analog [18F]2-deoxy-2-fluoro-D-glucose (FDG) is widely used for assessing regional myocardial glucose metabolism in vivo. The reproducibility of this method has recently been questioned because of a discordant affinity of hexokinase for its substrates glucose and 2-deoxyglucose. We therefore compared rates of glucose(More)
We postulated that glycogen is a significant energy substrate compared with fatty acids and glucose in response to adrenergic stimulation of working rat hearts. Oxidation rates were determined at 1-min intervals by release of 3H2O from [9,10-(3)H]oleate (0.4 mM, 1% albumin) and 14CO2 from exogenous [U-14C]glucose (5 mM) or, by a pulse-chase method, from(More)
Malonyl-CoA decarboxylase (MCD) catalyzes the degradation of malonyl-CoA, an important modulator of fatty acid oxidation. We hypothesized that increased fatty acid availability would increase the expression and activity of heart and skeletal muscle MCD, thereby promoting fatty acid utilization. The results show that high-fat feeding, fasting, and(More)
The mammalian myocardium meets its high energy needs through the oxidation of a variety of substrates, chiefly fatty acids. This review examines the hypothesis that efficient energy transfer in the heart occurs through a series of moiety-conserved cycles, which makes the heart an obligatory "omnivore." Ischemia results in a transformation of efficient(More)
We tested the hypothesis that glycogen is preferentially oxidized in isolated working rat heart. This was accomplished by measuring the proportion of glycolytic flux (oxidation plus lactate production) specifically from glycogen which is metabolized to lactate, and comparing it to the same proportion determined concurrently from exogenous glucose during(More)