74 III, OXIDATION AND METABOLISM 



these acids were shortened two carbons at a time, rather than by a single 

 carbon atom. Thus, phenylpropionic acid (C6H5-CH2-CH2-COOH) was 

 converted to benzoic acid rather than to phenylacetic acid.^ Had the 

 latter situation obtained, phenaceturio- acid would have been excreted; 

 actually hippuric acid was the end-product. When phenylbutyric acid 

 (C6H5-CH2-CH2-CH2-COOH) was fed, it was converted to phenyl- 

 acetic acid, which was subsequently eliminated as phenaceturic acid. 

 Here again, the rupture of the aliphatic fatty acid must have proceeded 

 two carbons at a time. Had the degradation occurred by single carbon 

 imits, then phenylpropionic acid would have originated from phenylbutyric 

 acid; the former acid is known to be oxidized to benzoic acid, which is 

 conjugated with glycine to appear in the urine as hippuric acid. How- 

 ever, no hippuric acid was present in the urine after the administration 

 of phenylbutyric acid, but only phenaceturic acid. Finally, Knoop^ 

 demonstrated that, when phenylvaleric acid (CeHs • CH2 • CH2 • CH2 • - 

 CH2 • COOH) was fed, it was oxidized to benzoic acid and was excreted as 

 hippuric acid. It was postulated that phenylvaleric acid is converted to 

 phenylpropionic acid, which is oxidized further to benzoic acid. 



Embden and co-workers^-^ demonstrated that the normal aliphatic 

 fatty acids undergo /3-oxidation in the same way as do the phenyl-substi- 

 tuted acids. Thus, when surviving livers were perfused with blood con- 

 taining hexanoic (caproic), octanoic (caprylic), or decanoic (capric) acids, 

 acetoacetic acid accumulated in the perfusate. On the other hand, aceto- 

 acetate could not be demonstrated in increased amounts in the blood after 

 odd-numbered acids had been added to the perfusing fluid. 



Dakin^"^* further supported the jS-oxidation theory on the basis of a 

 number of experiments in which intermediate products of the phenyl- 

 substituted fatty acids were recovered from the reaction mixture or from 

 the urine, and identified. Thus, when phenylpropionic acid was fed, or 

 injected, not only was it possible to isolate hippuric acid from the urine, 

 but/3-phenyl-i8-hydroxypropionic acid (C6H5-CHOH-CH2-COOH), benzo- 

 ylacetic acid (CeHs-CO-CHo-COOH), and acetophenone (CeHs • CO • CH3) 

 were also obtained. Intermediate compounds of other phenyl-substituted 



^ G. Embden, H. Salomon, and F. Schmidt, Beilr. chem. Physiol. Pathol., S, 129-155 

 (1906). 



8 G. Embden and A. Marx, Beitr. chem. Physiol. Pathol, 11, 318-322 (1908). 



9 H. D. Dakin, J. Biol. Chem., 4, 77-89 (1908). 

 JO H. D. Dakin, /. Biol. Chem,., 4, 91-100 (1908). 



" H. D. Dakin, J. Biol. Chem., 4, 227-233, 419-435 (1908). 

 12 H. D. Dakin, J. Biol. Chem., 5, 173-185, 303-309 (1908). 

 " H. D. Dakin, /. Biol. Chem., 6, 203-219, 221-233 (1909). 



