The rôle of adenosinetriphosphate in the activation of fatty acid oxidation in vitro.

The actual roles of the adenine nucleotides and activating factors such as the dicarboxylic acids of the Krebs cycle in the oxidation of fatty acids by broken cell preparations are unknown. Oxidation of the fatty acid (l-5) and the activating factor (6-8) leads to the synthesis of the phosphate bonds of adenosinetriphosphate.’ These facts have been difficult to demonstrate because of the rapid hydrolysis of ATP by the phosphatases present in the crude enzyme systems generally employed (2, 9, 10). In view of the rBle of ATP in glycolysis and in many synthetic reactions, it appears possible that ATP per se may be necessary in fatty acid oxidation, and that the dicarboxylic acids of the Krebs cycle may exert their activating effect by virtue of their ability to form ATP. However, it has been difficult to demonstrate that ATP per se is required for the oxidation of fatty acids in animal tissues, and only recently has evidence for the essential nature of this adenine nucleotide been obtained. Under proper conditions adenylic acid will serve as well as ATP for the oxidation of fatty acids (2, 6, 11, 12). On the other hand it has been recently shown that, in mitochondria with low ATPase activity, oxidation of octanoate is accelerated by the presence of phosphate acceptors such as the creatine-ATP or hexokinase systems. The more effective activation with the creatineATP system is attributed to the higher steady state concentration of ATP in the creatine system as compared to the hexokinase system (5). These results can be interpreted as evidence for the hypothesis that ATP per se may be necessary for the oxidation of fatty acids. Also ATP is required by a soluble fatty acid oxidase prepared from rat liver mitochondria (13). However, none of these experiments clarifies the relationship between the requirement for ATP and the requirement for activating factors such as members of the Krebs cycle. Previous studies (l-3, 6, 7, 14, 15) had