ACKTIC ACID AM) ACETATE 273 



Acetopyruvic acid is l)elieved to be immediately converted to acetoaeetic 

 acid in the liver, as follows: 



CH3COCH2COCOOH — ^ CII3COCH2COOH + CO2 

 AcetopjTuvic acid Acetoaeetic acid 



Conversion of Acetopyruvic Acid to Acetoaeetic Acid"^ 



Lehninger^'^ demonstrated the conversion of acetopyruvic acid to acetone 

 bodies in the intact rat, as well as in isolated tissues. Moreover, although 

 no liver glycogen was deposited in rats after the administration of this di- 

 keto acid, acetopyruvic acid was able to protect rats from toxic doses of 

 insulin. Lehninger suggests that this conversion to glucose may occur 

 during a critical demand on blood sugar. It is similar to the metabolic 

 fate of isoleucme, which Butts et al}^^ reported as being both ketogenic 

 and glucose-forming. When acetopyTu\'ic acid acts in its glucose-forming 

 capacity, the followong reaction may be postulated: 



CHsCO-CHzCOCOOH > CH3COCOOH -f- 2CO2 > Glucose 



Acetopyruvic acid Pyruvic acid 



The Mechanism of the Conversion of Acetopyruvic Acid to Glucose'^' 



However, several facts cause one to question whether or not acetopyruvic 

 acid can normally arise from the condensation of acetic and pyru\dc acids. 

 In the first place, pjTuvic acid has repeatedly been found to be a powerful 

 glycogenic agent, as well as one which is ketolytic in the presence of acetone 

 bodies.*^ Moreover, Weinhouse and collaborators** reported that labeled 

 octanoic acid is oxidized in such a way as to preclude the participation of 

 pyruvate in the synthesis of acetoacetate. It is therefore certain that 

 acetopyruvate is not an obligatory intermediate in ketone body formation; 

 in fact, it is highly improbable that the direct sjmthesis of this compound 

 from acetate and pjTuvate actually occurs m the tissues. 



(c) a-Ketoglutaric Acid. According to Krebs,^'* when an "end-to-end" 

 condensation of acetic and p\Tuvic acids occurs, a-ketoglutarate is the 

 compound which results. On the basis of his findings, the follo^^ing equa- 

 tion to illustrate this change is suggested: 



HOOCCH.iH + HICH.COCOOH * HOOCCH2CH2COCOOH + 2H 



Acetic acid P\TUvic acid a-Ketoglutaric acid 



Synthesis of a-Ketoglutaric Acid by Dehj'drogenative Coupling of Acetic and Pyruvic 



Acids'^ 



1" A. L. Lehninger, ./. Biol. Chem., 148, 39.3-404 (1943). 



»'^ J. S. Butts, H. Blunden, and M. S. Dunn, J. Biol. Chem., 120, 289-295 (1937). 

 >35 H. A. Krebs, Nature, 138, 288-289 (1936). 



i'« S. Weinhouse, G. Medes, X. F. Floyd, and L. Noda, /. Biol. Chem., 161, 745-746 

 (1945). 



