76 III. OXIDATION AND METABOLISM 



this finding, Qiiick^^ reported that phenylacetic acid, when administered 

 as such, or when formed after the feeding of phenylbutyric acid or of 

 phenylisocrotonic acid (C6H5-CH:CH-CH2-COOH), is conjugated with 

 glucuronic acid and with glycine in the ratio of 1:2. In the later study, 

 Quick^^ reported that the conjugation of newly formed benzoic acid with 

 glucuronic acid and with glycine is 2:1 after the feeding of phenylvaleric 

 acid, phenyl-a,/5-pentenic acid (C6H5-CH2-CH2-CH:CH-COOH) or 

 phenyl-/3-7-pentenic acid (C6H5-CH2-CH:CH-CH2-COOH). The iden- 

 tity of the proportion of glucuronic acid and glycine used for the de- 

 toxication of benzoic acid and phenylacetic acid, irrespective of whether 

 these aromatic acids were fed as such or whether they originated by oxida- 

 tion of the aliphatic side chain, ^^'^^ offers especially strong confirmation of 

 the /3-oxidation hypothesis. 



Attention should likewise be called to the studies of Raper and Wayne, ^^ 

 who fed phenylpropionic, phenylbutyric, phenylvaleric, and phenylcaproic 

 acids to dogs, and noted that the end-products formed were in harmony 

 with those one would expect according to the /3-oxidation theory. How- 

 ever, w^hen phenylnonanoic acid (CeHs- (CH2)8-COOH) or phenyldecanoic 

 acid (C6H5-(CH2)9-COOH) was fed, the amount of benzoic and of phenyl- 

 acetic acids formed, respectively, was less than that calculated from the 

 phenyl residues involved. It is therefore suggested that, in addition to /?- 

 oxidation, some other type of breakdown obtains in the case of long-chain 

 aliphatic acids. 



However, the results of Quick ^^ throw some doubt on the hypothesis 

 that the /S-hydroxy and |S-keto acids are normal intermediates in fatty acid 

 oxidation. Since phenyl-;S-hydroxypropionic acid (C6H5-CHOH-CH2-- 

 COOH) is excreted largely michanged by dogs, and only 25% is oxidized 

 to benzoic acid, there is some question as to whether or not it is a normal 

 intermediary product in the oxidation of phenylpropionic acid. More- 

 over, the proportion of newly-synthesized benzoic acid formed after the 

 feeding of phenylpropionic acid which is detoxicated with glucuronic acid 

 and with glycine was found to be 1 : 1, in sharp contrast to the 3 : 1 ratio of 

 these components when benzoic acid itself was administered. 



Acetophenone (CgHb • CO • CH3) , the ketone formed when jS-ketopropionic 

 acid is heated, is partially changed to benzoic acid and partially reduced to 

 phenylmethylcarbinol (CeHe-CHOH-CHs). In this case, the benzoate is 

 largely conjugated with glycine. According to Quick, ^^ this phenomenon 

 obtains because of the slow rate of production of benzoic acid. These 

 experiments confirm the earlier results of Thierf elder and Daiber.'" 



" H. S. Raper and E. J. Wayne, Biochem. J., 22, 188-197 (1928). 



20 H. Thierfelder and K. Daiber, Z. physiol. Chenu, 130. 380-396 (1923). 



