166 III. OXIDATION AND METABOLISM 



that the pyruvate effect might be due to a coudensation of the pyruvate 

 with acetaldehyde (arising from the oxidation of alcohol) to give acetoin 

 (CHs-CO-CHOH-CHs). It was also evident from the report of Leloir 

 and Munoz^i^ that pyruvate could augment the oxidation of alcohol by 

 liver slices. Dontcheff^^" likewise observed, by study of the whole animal, 

 that the feeding of large doses of carbohydrate to fasted rats stimulated 

 alcohol oxidation. Carpenter and Lee,^^^ in tests of human subjects, 

 found that alcohol was metabolized more rapidly when given with glucose 

 or fructose than when galactose was ingested. 



In a later study, Westerfeld, Stotz, and Berg^22 presented evidence that 

 the increased utilization of alcohol in the presence of pyruvate was, in fact, 

 a coupled oxidation-reduction reaction between pyruvate and alcohol. 

 Von Euler and Adler^^s g^j^^j Quibell^^^ had established the fact that this is 

 a coenzyme-linked reaction in which both the oxidation of alcohol and the 

 reduction of pyruvate^^^ are dependent upon the presence of diphospho- 

 pyridine nucleotide (coenzyme I). 



Acetoin is the coupled reaction product arising when an animal carbox- 

 ylase system acts upon pyruvate and alcohol or acetaldehyde. Berg and 

 Westerfeld^^" reported that pyruvate and propionaldehyde also react to 

 give a 5-carbon ketol, by condensation of the 2-carbon fragment of decar- 

 boxylated pyruvate with 3-carbon propionaldehyde. 



b'. The Tricarboxylic Acid Cycle and the Oxidation of Ketone Bodies: 

 The present concept is that oxaloacetic acid is the active agent in combining 

 with acetoacetate, thus bringing the latter into the tricarboxylic cycle 

 (citric acid cycle), and so effecting the oxidation of ketone bodies. As 

 early as 1891, Claisen and Hori^" described the condensation of oxaloacetic 

 acid and acetic acid by the aldol method to yield citric acid. It is now 

 accepted that the action of acetic and acetoacetic acid in the formation of 

 citric acid resembles that of oxaloacetate, and that presumably they yield 

 a similar active condensing agent. Although Breusch^^^ postulated the 

 enzymatic synthesis of citric acid from oxaloacetic acid two years before 



"9 L. F. Leloir and J. M. Muiioz, Biochem. J., 32, 299-307 (1938). 

 620 L. Dontcheff, Compt. rend. soc. bioL, 126, 462-464, 465-467 (1937). 

 "1 T. M. Carpenter and R. C. Lee, /. Pharmacol. Exptl. Therap., 60, 254-263, 264-285, 

 286-295 (1937). 



"2 W. W. Westerfeld, E. Stotz, and R. L. Berg, /. Biol. Chem., 149, 237-243 (1943). 



"3 H. von Euler and E. Adler, Z. physiol. Chem., 226, 195-212 (1934). 



"<T. H. QuibeU, Z. physiol. Chem., 251, 102-108 (1938). 



"5 D. E. Green and J. Brosteaux, Biochem. J., 30, 1489-1508 (1936). 



626 R. L. Berg and W. W. Westerfeld, /. Biol. Chem., 152, 113-118 (1944). 



6"L. Claisen and E. Hori, Ber., 24, 120-127 (1891). 



"8 F. L. Breusch, Z. physiol. Chem., 250, 262-280 (1937). 



