TRIGLYCERIDES AND FATTY ACIDS 101 



tern, which requires a fatty acid with at least one double bond as a sub- 

 strate, and which catalyzes the reaction at a greatly augmented rate with a 

 diethenoid acid, is called lipoxidase. In addition to the oxidase systems, the 

 closely related dehydrogenases are hkewise important in the oxidation reac- 

 tion. Phillips and Williams^^^ reported the presence of an oxidative system 

 ill chicken fat. 



a. Fatty Acid Oxidase Systems, (a) Fatty Acid Oxidase of Lehninger. 

 Although the oxidation of fatty acids by the liver tissue of the intact 

 animal, and even by isolated liver slices, has been reported many times, 

 Muiioz and Leloir^^ were the first to demonstrate the oxidation of fatty 

 acids by cell-free preparations of the liver. These workers found that, when 

 butyrate was incubated with particulate matter from guinea pig liver, to 

 which Mg++, cytochrome-c, orthophosphate, adenylic acid and an inter- 

 mediate from the Krebs tricarboxylic acid cycle were added, an oxidation 

 with molecular oxygen occurred. The enzyme system was extremely 

 labile, and in only a few cases could oxidation of higher acids, such as oc- 

 tanoic acid, be demonstrated. The ketone bodies were the principal oxida- 

 tion products. 



In 1944, Lehninger i^'^'i^^ first demonstrated independently that saturated 

 fatty acids from C4 to Cis could be oxidized by homogenates of rat liver sup- 

 plemented with cytochrome-c, in calcium-free saline. This preparation 

 proved to be much more stable than that of Munoz and Leloir.^^ Shortly 

 after the discovery of the oxidation system, Lehninger ^^^ demonstrated that 

 the activity resided in an easily-sedimented particulate fraction of the 

 homogenate. After separation and washing, this fraction oxidized fatty 

 acids without significant endogenous oxygen uptake, provided that Mg++, 

 ATP, and orthophosphate were present. This fraction brought about a 

 practically complete oxidation of fatty acids to ketone bodies, but the 

 system did not have the capacity to oxidize the latter compounds. ^^^ 

 Lehninger '^^•'•*'' made the important observation that, if oxaloacetate, fuma- 

 rate, or malonate was added to the incubation mixture, the yield of aceto- 

 acetate was decreased, and some of the fatty acid carbon became incor- 

 porated into citrate, a-ketoglutarate, and succinate. On the basis of proof 

 obtained in studies with isotopically-labeled fatty acids that fatty acids 

 are broken down to two-carbon fragments, ^^^ it was suggested that the ac- 



"5 H. J. Phillips and I. L. Williams, Science, 117, 658-659 (1953). 



'^ A. L. Lehninger, /. Biol. Chem., 154, 309-310 (1944). 



1" A. L. Lehninger, J. Biol. Chem., 157, 363-381 (1945). 



'^ A. L. Lehninger, J. Biol. Chem., 161, 437-451 (1945). 



"^ A. L. Lehninger, J. Biol. Chem., 164, 291-306 (1946). 



1^ A. L. Lehninger, J. Biol. Chem., 161, 413-414 (1945). 



"> S. Weinhouse, G. Medes, and N. F. Floyd, J. Biol. Chem., 155, 143-151 (1949). 



