136 III. OXIDATION AND METABOLISM 



liver.'^'^ Neither phenylalanine^^^ nor tyrosine^^''^-^ yields sugar when fed 

 to phlorhizinized dogs. 



On the other hand, Butts and associates'-^ were unable to demonstrate 

 any ketonuria when either DL-phenylalanine or DL-tyrosine was fed to fast- 

 ing rats. The amino acids appeared to have different metabolic pathways. 

 Thus, phenylalanine gave rise to glycogen, and reduced an exogenous 

 ketonuria, while tyrosine exerted no such effect. Moreover, homogentisic 

 acid was excreted after the administration of phenylalanine, but not after 

 that of tyrosine.'^* 



Further proof that tyrosine is capable of conversion to acetoacetic acid 

 has been recorded by Weinhouse and Millington.'^''''*^ It was suggested 

 that the data indicate that the a- and jS-carbons of tyrosine become the 

 carboxyl and a-carbon of acetoacetate, respectively. Two of the carbons 

 in the benzene ring become the (8- and 7-carbons in acetoacetate. It is 

 interesting that Wakeman and Dakin,^^- many years before isotopic tech- 

 nics were available, suggested that two of the four carbons of acetoacetate 

 are probably derived from the phenyl ring, and two from the side-chain. 

 In view of the conflicting evidence presented by several investigators, it 

 is probably better at the present time to reserve judgment as to whether or 

 not phenylalanine and tyrosine are ketogenic. 



g'. Miscellaneous Amino Acids: Edson'^^ reported that a-aminobutyric 

 acid, CH3-CH2-CH(NH2)-COOH, is sHghtly ketogenic, while Cohen'«2 

 found that this amino acid is toxic for liver slices. a-Aminovaleric acid, 

 CH3 • CH2 • CH2 • CH(NH2) • COOH, was shown, by the liver shce technic, to 

 be ketogenic, while a-aminocaproic acid, CH3-CH2-CH2-CH2-CH(NH2) • 

 COOH, gave negative results.'"- Cohen,'"- using the hver slice technic, 

 demonstrated that, of the branched-chain a-amino acids, a-aminoisobutyric 

 acid, (CH3)2:C(NH2)- COOH, is toxic, a-aminoisovaleric acid, (CH3)2:CH-- 

 CH(NH2) -COOH, is not ketogenic, while a-aminoisocaproic acid, (CH3)2:- 

 CH-CH2-CH(NH2)-COOH, is ketogenic. The ^-hydroxy- and a-keto 

 acids of the normal and branched a-amino acids behaved in a manner 

 similar to that of their parent amino acids. '"- 



{g) Formation from Pyruvate. There have been a number of reports in 

 the literature to the effect that acetic acid is formed in the animal body from 

 pyruvate (see discussion in Chapter V). Since acetoacetate can readily 



327 M. Hensel and R. Riesser, Z. physiol. Chem., 88, 38-43 (1913). 



328 A. J. Ringer and G. Lusk, Z. physiol Chem., 66, 106-119 (1910). 



32S J. S. Butts, M. S. Dunn, and L. F. Hallman, J. Biol. Chem., 123, 711-718 (1938). 



330 S. Weinhouse and R. H. Millington, /. Biol. Chem., 175, 995-996 (1948). 



331 S. Weinhouse and R. H. MilUngton, /. Biol. Chem., 181, 645-653 (1949). 



332 A. J. Wakeman and H. D. Dakin, /. Biol. Chem., 9, 139-150 (1911). 



