Studies on the cyclophorase system: XXV. Fatty acid oxidation in the rabbit liver system

A study has been made of fatty acid oxidation in the cyclophorase-mitochondrial system of rabbit liver with particular reference to the mechanism of acetoacetate formation: 1. 1. The oxidation of fatty acids and their β-hydroxy derivatives to CO 2 and H 2O is inhibited by fluoride, whereas the conversion of β-hydroxybutyrate to acetoacetate by β-hydroxybutyric dehydrogenase is not affected. 2. 2. For even-numbered fatty acids the molar ratio of acetoacetate formed to substrate metabolized approaches 1 at C 6 and may exceed 1 at C 8 and higher (upper limit 1.5). 3. 3. For the lower odd-numbered fatty acids acetoacetate formation is very small. For C 9 and C 11, about 0.5 mole of acetoacetate is formed per mole of fatty acid oxidized. 4. 4. The ratio of carbonyl to carboxyl label in the acetoacetate produced from the carboxyl-labeled C 4 to C 8 acids is found to increase steadily from 0.3 to 0.8. 5. 5. The oxidation of even-numbered fatty acids proceeds in a similar manner in preparations from rat and pigeon liver. No oxidation of odd-numbered acids was, however, observed with rat liver. 6. 6. The inhibition of fatty acid oxidation by malonate can be overcome by addition of members of the citric acid cycle in relatively high concentration. Under these conditions fatty acids are almost quantitatively converted to acetoacetate. 7. 7. The oxidation of longer chain acids proceeds at a low rate as demonstrated with labeled C 16 and C 18, 8. 8. Odd-numbered fatty acids have an inhibitory effect on acetoacetate formation from even-numbered acids when oxidized simultaneously. 9. 9. Possible mechanisms which explain the mode of acetoacetate formation and the distribution of label in acetoacetate are discussed. Le présent travail se rapporte à l'oxydation des acides gras dans le système de cyclophorase provenant des mitochondries du foie de lapin. Une attention toute particulière a été portée au mécanisme de formation de l'acétoacétate. 1. 1. Les fluorures inhibent l'oxydation des acides gras et de leurs dérivés β-hydroxyle; cependant ils sont sans effet sur la transformation du β-hydroxybutyrate en acétoacétate par la déhydrogénase β-hydroxybutyrique. 2. 2. Dans le cas des acides gras à nombre pair d'atomes de carbone le rapport des concentrations molaires d'acétoacétate produit et de substrat métabolisé s'approche de l'unité pour une chaîne en C 6. Ce rapport s'élève au dessus de l'unité pour les chaînes en C 8 on plus (limite supérieure 1.5). 3. 3. Les acides gras