TRIGLYCERIDES AND FATTY ACIDS 137 



be formed from acetate, it would appear that pyruvate can be considered 

 as one of the parent substances of the ketone bodies. 



Moreover, there is direct evidence that acetoacetate can accumulate in 

 amounts up to 28% of that of the pyruvate oxidized^'*-^^^ when liver slices 

 break down pyruvate in the presence of malonate^*' or of ammonium 

 chloride.^'^ Moreover, pyruvate is quantitatively converted to aceto- 

 acetate by the washed-cell liver preparation of Lehninger,^-'^^ When 

 fumarate was added to the washed-cell preparations, acetoacetate forma- 

 tion was suppressed^"*" in favor of a greater production of di- and tricarbox- 

 ylic acids. Since the in vitro conditions which affect the relative yields of 

 acetoacetate and the polycarboxylic acids were the same for octanoic acid 

 and for pyruvic acid, it was believed that an acetyl-like C2 compound was 

 common to both fats and carbohydrates. 



In a later study of the parallel behavior of octanoate and pyruvate with 

 Lehninger's preparation, Crandall and Gurin^' found that only the a- 

 and j8-carbons of pyruvate become incorporated into the acetoacetate mole- 

 cule. However, octanoate differed from pyruvate in the production of 

 asymmetrically-labeled acetoacetate from carboxyl-labeled octanoic acid. 

 When the octanoate was labeled on the carboxyl or /3-carbon, acetoacetate 

 was produced, with more C'^ in the carboxyl than in the carbonyl group. ^^^ 

 On the other hand, when f-labeled octanoate was incubated with liver 

 homogenate, the acetoacetate formed was predominantly labeled in the 

 carbonyl group. ^^^ It is suggested that the fatty acids, on oxidation, give 

 rise to two species of C2 fragments in the formation of acetoacetate; one 

 of these, which is not readily acetylated, is derived from the f- and oj- 

 carbons of octanoate, while the other type originates from the first six car- 

 bons of octanoate. The terminal fragment has a tendency to acetylate 

 rather than to be acetylated. One possibility which is suggested is that 

 pyruvate and acetate form two C units which are identical with the two C 

 units derived from the first six carbons of octanoate. ^^^ Shreeve^^^ has 

 likewise reported that propionate is as effective as pyruvate as a precursor 

 of acetyl groups in the intact rat. 



However, the conversion of pyruvate to acetoacetate in the normal ani- 

 mal appears highly improbable. It will be observed that the only condi- 

 tions in which this change has been observed are in in vitro tests where an 

 abnormal metabolite is present which causes an alteration in the usual 



3" E. Annau, Z. physiol. Chem., 224, 141-149 (1934). 



3" N. L. Edson, Biochem. J., 29, 2082-2094 (1935). 



"5 E. A. Evans, Jr., Biochem. J., 34, 829-837 (1940). 



336 D. I. Crandall, R. O. Brady, and S. Gurin, /. Biol. Chem., 181, 845-852 (1949), 



»' W. W. Shreeve, /. Biol. Chem., 195, 1-10 (1952). 



