138 III. OXIDATION AND METABOLISM 



course of metabolism. Moreover, Weinhouse and Millington^"^ concluded 

 that, in contrast to its action in homogenates of liver, pyruvate does not 

 significantly increase acetoacetate production in liver slices. It is also 

 suggested that pyruvate is not ketogenic in the intact normal liver cell. 

 Bloch^*^ likewise points out that, in spite of the evidence that pyruvic acid 

 is a source of ketone bodies, this reaction is contrary to results obtained 

 with intact animals. Pyruvate has the ability to yield glycogen and to 

 suppress ketonuria in the fasting rat,^*" whereas fatty acids provoke a 

 ketonuria. Under such conditions the catabolites of fat and pyruvate do 

 not follow a single pathway. The derivation of acetoacetate from pyru- 

 vate may be a favored reaction under special conditions in vitro; however, 

 if it occurs at all, it is quantitatively insignificant in the pyruvate metab- 

 olism of the intact animal. Bloch concludes that "The hypothesis that 

 a C2 fragment arises in the oxidation of both carbohydrate and fat would 

 seem to be untenable unless it is assumed that the C2 fragments are not 

 identical." 



In a number of reactions the behavior of pyruvate differs from that of 

 fatty acids. Thus, whereas acetate serves as an excellent source of the 

 acetyl group for both aromatic amines (such as sulfanilamide) and for a- 

 amino acids (such as phenylaminobutyric acid), pyruvate, when admin- 

 istered as tagged alanine, can acetylate a-amino acids only.'^i Another 

 difference is that pyruvate (alanine) does not serve as a building stone for 

 cholesterol either in vivo^*^ or in vitro.^*- An additional variation between 

 the physiologic behavior of acetate and that of lactate (which is in equilib- 

 rium with pyruvate) is that acetate may serve as the source of carbons 

 2 and S in the purine imcleus, while lactate cannot be incorporated into the 

 uric acid molecule. Thus, if pyruvic acid or lactic acid were converted to 

 the same C2 fragment which originates from acetate, they should mediate 

 identical reactions in the acetylation of aromatic amines and in the synthe- 

 sis of cholesterol and of uric acid. Since this does not occur, one must con- 

 clude that no important part of pyruvate metabolism proceeds by way of 

 the acetyl group. 



(h) Formation from Dicarhoxylic Acids. On the basis of studies with 

 liver slices, Edson^"*^ concluded that the dicarboxylic acids are not ketogenic. 



338 S. Weinhouse and R. H. Millington, J. Biol. Chem., 193, 1-10 (1951). 



339 K. Bloch, Physiol. Revs., 27, 574-620 (1947). 

 3« I. Shapiro, J. Biol. Chem., 108, 373-387 (1935). 



3" K. Bloch and D. Rittenberg, J. Biol. Chem., 159, 45-58 (1945). 



342 D. Rittenberg, E. Borek, and K. Bloch, Federation Proc, 5, 151 (194G). 



3« N. L. Edson, Biochem. J., 30, 1855-1861 (1936). 



