Date of Degree
The effects of metabolic intermediates and coenzymes on the activities of fatty acyl-CoA synthetase and carnitine palmitoyltransferase (CPT) in rat heart mitochondria were studied. ADP and palmitoyl-l-carnitine were weak inhibitors of fatty acyl-CoA synthetase. CPT A was inhibited 59.3% by 100 (mu)M succinyl-CoA. However, succinate thiokinase activity in rat heart cytosol was too low to maintain a succinyl-CoA concentration sufficient to affect the activity of CPT A. There was no indication that fatty acid oxidation in rat heart mitochondria is controlled via the regulation of either CPT A or fatty acyl-CoA synthetase.
The dependence of the oxidation of unsaturated fatty acids containing cis double bonds on the presence of 3-hydroxyacyl-CoA epimerase was investigated. The specific activity of epimerase in rat heart mitochondria was found to be significantly lower than the rate of linoleoyl-CoA oxidation. Thus, it is the NADPH-dependent 2,4-dienoyl-CoA reductase, not the 3-hydroxyacyl-CoA epimerase, which functions in the oxidation of polyunsaturated fatty acids. C.-H. Chu, L. Kushner, D. Cuebas, and H. Schulz, Biochem. Biophys. Res. Comm., vol. 118, pp. 162-167, 1984 .
3-Mercaptopropanoyl-CoA and S-acetyl-3-mercaptopropanoyl-CoA, physiological metabolites of the known convulsant 3-mercaptopropanoic acid, were examined for their effects on purified pyruvate dehydrogenase complex from porcine and bovine heart. Both 3-mercaptopropanoyl-CoA and S-acetyl-3-mercaptopropanoyl-CoA were found to be inhibitors of this enzyme. Under optimal conditions, 50% inhibition was obtained at 12.6 (mu)M 3-mercaptopropanoyl-CoA or 5.2 (mu)M S-acetyl-3-mercaptopropanoyl-CoA while 100 (mu)M of the latter compound gave 90% inhibition. The inhibition observed with S-acetyl-3-mercaptopropanoyl-CoA was demonstrated to be irreversible. Maximal inhibition of the complex and its component enzymes was observed when it was reacted with the inhibitor under conditions which promote reduction of the endogenous lipoate. L. Kushner, D. Cuebas, and H. Schulz, Fed. Proc., vol. 43(7), pp. 1870, 1984 .
Preliminary results indicate that S-acetyl-3-mercaptopropanoyl-CoA formed intramitochondrially inhibits pyruvate-supported respiration in rat heart and liver mitochondria.
Kushner, Leslie, "Aspects of Mitochondrial Oxidative Metabolism" (1985). CUNY Academic Works.