Studies of fatty acid oxidation. 3. The effects of acyl-CoA complexes on fatty acid oxidation.

The oxidation of fatty acids to acetoacetate or to carbon dioxide is affected by the presence of various aliphatic and aromatic acids. For example, benzoate inhibits acetoacetate formation from butyrate at low concentrations in guinea pig liver slices (Jowett & Quastel, 1935b) and in 'cyclophorase' preparations (Grafflin & Green, 1948). Benzoate also inhibits the oxidation of butyrate to C02 in guinea pig liver slices (Avigan & Scholefield, 1954) and the oxidation of alkylthio fatty acids to C02 in rat-liver slices (Brown & Scholefield, 1954). Again, propionate markedly inhibits the formation of acetoacetate frombutyrate, in guinea pig liver slices, where it is rapidly oxidized (Quastel & Wheatley, 1933). Liver 'cyclophorase'preparations, when well washed, do not oxidize propionic or phenylpropionic acid (Grafflin & Green, 1948), but in such preparations the presence of propionate still produces an inhibition of acetoacetate synthesis from -acetate (Lang & Bassler, 1953). It follows, therefore, that propionate exercises its inhibition by a mechanism other than by formation of pyruvate. The alkylthio fatty acids also inhibit acetoacetate formation from acetate and butyrate in guinea pig liver slices, probably by first forming CoA derivatives (Avigan & Scholefield, 1954). Similarly, benzoate may inhibit acetoacetate synthesis as a result of benzoyl-CoA formation. The purpose of the present paper is to throw light on the mechanism of inhibition of acetoacetate synthesis by acyl-CoA complexes and to offer an explanation ofthe effects ofvarious carboxylic acids on fatty acid metabolism. An attempt will also be made to explain the fact that, in presence of sources of oxaloacetate, the long-chain fatty acids have a greater tendency than the short-chain fatty acids to be oxidized through the citric acid cycle (Kennedy & Lehninger, 1950).