ACETIC ACID AND ACETATE 261 



to the washed-cell preparations, acetoacetate formation was suppressed 

 in favor of a greater production of di- and tricarboxylic acids. Since the 

 in vitro conditions which affected the relative yields of acetoacetate and 

 polycarboxyhc 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. 



Bloch^ points out that, in spite of the evidence from in vitro tests that 

 pyruvic acid under certam conditions is a source of ketone bodies, this 

 reaction is contrary to known data obtamed with intact animals. Pyruvate 

 has the ability to yield glycogen and to suppress ketonuria in the fasting 

 rat,^^ whereas even-chain fatty acids provoke a ketonuria. Under such 

 conditions the catabolites of fat and pyi'uvate do not follow a single path- 

 way. The derivation of acetoacetate from pyruvate may be a favored 

 reaction under special conditions in vitro; however, if it occurs at all, it is 

 quantitatively msignificant in the pyruvate metabolism of the intact 

 animal. Bloch^ concludes that "The hypothesis that a C2 fragment arises 

 hi the oxidation of both carbohydrate and fat would seem to be untenable 

 unless it is assumed that the C2 fragments are not identical." 



There are a number of reactions in which the behavior of pyruvate 

 differs from that of fatty acids. Thus, whereas acetate serves as an excel- 

 lent source of the acetyl group both for aromatic amines (such as sulfanila- 

 mide) and for a-amino acids (such as phenylaminobutyric acid), pyruvate, 

 when administered as tagged alanine, can acetylate a-amuio acids only.^^ 

 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 physiological behavior of acetate and that of lactate (which is 

 in equihbrium with pyruvate) is that acetate may serve as the source of 

 carbons 2 and 8 in the purme nucleus, while lactate cannot be incorporated 

 into the uric acid molecule. Thus, if pyruvic acid or lactic acid were con- 

 verted to the same C2 fragment as originates from acetate, then should 

 show identical reactions m the acetylation of aromatic ammes and in the 

 sjaithesis of cholesterol and uric acid. Since this does not occur, one must 

 conclude that no important part of pyruvate metabolism proceeds by way 

 of the acetyl group. 



d. Formation from Amino Acids. It is generally recognized that a- 

 araino acids are usually deaminated with the formation of an a-keto acid; 

 this is followed by decarboxylation, with the ultimate formation of a fatty 

 acid having one less carbon than the original amino acid. This non- 

 nitrogenous moiety is subsequently oxidized in a manner similar to that of 



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



" D. Rittenberg, E. Borek, and K. Bloch, Federation Proc, 5, 151 (1946). 



