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Reversible Inhibition of Mitochondrial Adenosine Diphosphate Phosphorylation by Long Chain Acyl Coenzyme A Esters

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      Palmitoyl coenzyme A instantly and reversibly inhibited the electron transport-linked phosphorylation of ADP coupled to the oxidation of various substrates by rat heart mitochondria. The inhibitory effectiveness of palmitoyl-CoA was dependent on mitochondrial as well as ADP concentration. Removal of palmitoyl-CoA, such as by its oxidation following (—)-carnitine addition, led to a restoration of ADP-coupled mitochondrial oxidations. Excess of ADP also reversed the palmitoyl-CoA inhibition, whereas ATP, AMP, and guanosine diphosphate were ineffective. Dinitrophenol overcame the palmitoyl-CoA-imposed inhibition of mitochondrial oxidation. Palmitoyl-CoA also inhibited the dinitrophenol-stimulated mitochondrial adenosine triphosphatase activity, whereas (—)-palmitoylcarnitine and lauryl sulfate did not show a comparable kind of effect, and oleate was relatively ineffective. However, palmitoyl-CoA did not inhibit the mitochondrial adenylate kinase or the palmitate-activating enzyme. Palmitoyl-CoA thus behaved like atractyloside, suggesting the site of its inhibition to be at the adenine nucleotide translocase. In agreement was the observation that palmitoyl-CoA decreased the affinity of the mitochondrial phosphorylation system for added ADP. CoA, acetyl-CoA, (—)-palmitoylcarnitine, oleate, or lauryl sulfate did not reveal a type of inhibition of ADP-supported mitochondrial oxidations shown by palmitoyl-CoA or stearoyl-CoA.
      It is possible that this inhibition of mitochondrial ADP phosphorylation by long chain acyl-CoA esters beregulate the proportioning of long chain acyl-CoA esters between their utilization for oxidation and for glyceride formation depending upon the availability of free fatty acids and the existing energy needs of the cell.

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