Reversible inhibition of mitochondrial adenosine diphosphate phosphorylation by long chain acyl coenzyme A esters.

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 pahnitoyl-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. Pahnitoyl-CoA also inhibited the dinitrophenol-stimulated mitochondrial adenosine triphosphatase activity, whereas (-)-pahnitoylcarnitine and lauryl sulfate did not show a comparable kind of effect, and oleate was relatively ineffective. However, pahnitoyl-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 pahnitoyl-CoA decreased the affinity of the mitochondrial phosphorylation system for added ADP. CoA, acetylCoA, (-)-pahnitoylcarnitine, oleate, or lauryl sulfate did not reveal a type of inhibition of ADP-supported mitochondrial oxidations shown by pahnitoyl-CoA or stearoyl-CoA. It is possible that this inhibition of mitochondrial ADP phosphorylation by long chain acyl-CoA esters serves to regulate 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.