Regulation of long chain fatty acid activation in heart muscle.
Regulation of fatty acid activation was studied in whole tissue homogenates of rat heart. The palmityl-CoA synthestase activity was proportional to the fatty acid to albumin ratio in the incubation medium with maximal activity occurring at a molar ratio of about 5. Fatty acyl-CoA synthetase activity was inhibited by products of the reaction (AMP, pyrophosphate, and palmityl-CoA). The apparent Ki for palmityl-CoA inhibition was 5 muM and this inhibition could be relieved by CoA-SH or albumin. The Km for CoA-SH in the absence of palmityl-CoA was 7 muM and was increased to 24 muM by addition of 8 muM palmityl-CoA. Cytosolic and mitochondrial levels of CoA-SH and carnitine were estimated in whole tissue homogenates of heart and liver. From 90 to 100% of whole tissue CoA was recovered in the mitochondrial fraction of heart muscle and it was estimated that the cytosolic concentration of free CoA-SH probably never exceeds its Km value for fatty acid activation in this tissue. Therefore, the rate of fatty acid activation would be expected to depend on the availability of CoA-SH in the cytosolic space. By adjusting the concentration of CoA-SH in the cytosol to the rate of acetyl-CoA oxidation, carnitineacetyl-CoA transferase may function in cardiac muscle to couple the rate of fatty acid activation in the cytosolic compartment to acetyl-CoA oxidation in the mitochondria. Approximately 30% of whole tissue CoA-SH was located in the cytosolic space in liver. Heart muscle has about twice as much carnitine as liver but in both tissues 100% of whole tissue carintine was located in the cytosolic space. The ratio of carnitine to CoA-SH in the cytosolic space was estimated to be about 100 in heart and 17 in liver. This high ratio in cardiac muscle may function to channel fatty acids toward oxidation rather than toward synthesis of complex lipids.
D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism; D002331:Carnitine / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003065:Coenzyme A; D003600:Cytosol / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D010169:Palmitic Acids / Q000378:metabolism; D010477:Perfusion; D011422:Propionates; D051381:Rats
D005230:Fatty Acids, Nonesterified; D010169:Palmitic Acids; D011422:Propionates; D005969:Glutamate Dehydrogenase; D000123:Acetyltransferases; D064429:Fatty Acid Synthases; D002950:Citrate (si)-Synthase; D002262:Carboxy-Lyases; D002331:Carnitine; D003065:Coenzyme A