REGULATION OF ACYL-COENZYME-A DEHYDROGENASES AND FATTY ACID OXIDATION IN HEART.
Item
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Title
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REGULATION OF ACYL-COENZYME-A DEHYDROGENASES AND FATTY ACID OXIDATION IN HEART.
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Identifier
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AAI8508693
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identifier
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8508693
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Creator
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DAVIDSON, BRUCE PAUL.
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Date
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1985
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Language
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English
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Publisher
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City University of New York.
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Subject
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Chemistry, Biochemistry
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Abstract
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Bovine liver butyryl-CoA dehydrogenase, general acyl-CoA dehydrogenase and long-Chain acyl-CoA dehydrogenase, all of which are believed to function in fatty acid oxidation, have been separated and partially purified by a simple two-step procedure. The same procedure was used to separate the bovine heart acyl-CoA dehydrogenases. Butyryl-CoA dehydrogenase, general acyl-CoA dehydrogenase and long-chain acyl-CoA dehydrogenase were thus identified and found to be identical with the bovine liver enzymes.;The control of B-oxidation via the regulation of acyl-CoA dehydrogenase has been investigated. All three acyl-CoA dehydrogenases are strongly inhibited by 3-ketoacyl-CoA's and less so by 2-enoyl-CoA compounds. However, most severely inhibited is long-chain acyl-CoA dehydrogenase, which may catalyze the first step in the oxidation of long-chain fatty acids. The following inhibition constants were determined with long-chain acyl-CoA dehydrogenase: K(,I) = 1.3 (mu)M and K(,I) = 0.075 (mu)M for 3-ketodecanoyl-CoA with palmitoyl-CoA and decanoyl-CoA as substrates, respectively; K(,I) = 0.2 (mu)M for 3-ketopalmitoyl-CoA with palmitoyl-CoA as a substrate.;It is proposed that a decrease in the energy demand of heart muscle leads to an increased concentration of acetyl-CoA which causes the inhibition of 3-ketoacyl-CoA thiolase (Y. Olowe and H. Schulz (1980) Eur. J. Biochem. 109, 425-429). The consequence of an inhibition of 3-ketoacyl-CoA thiolase may be an accumulation of 3-ketoacyl-CoA compounds which would inhibit most effectively long-chain acyl-CoA dehydrogenase, the enzyme that presumably catalyzes the first step of B-oxidation.;In order to determine the presence of fatty acid oxidation intermediates in mitochondria, coupled rat heart mitochondria were incubated for 2 min with 16-('14)C palmitoyl-CoA at state 3 and state 4 respiration. At state 4, in contrast to state 3 respiration large amounts of hydroxy acids, presumably in the form of their CoA derivatives, accumulated. Identification and quantitation of methyl ketones derived from 3-ketoacyl-CoA's provided evidence for a 3-fold increase in their concentration to 3mM when the respiration state was changed from 3 to 4. These observations support the hypothesis that (beta)-oxidation may be controlled via the regulation of long-chain acyl-CoA dehydrogenase by 3-ketoacyl-CoA and possibly 2-enoyl-CoA compounds.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
