BRANCHED-CHAIN ACIDS 293 



their results. Thus, the oxidation of a-phenylpropionic acid to yield 

 phenylacetic acid was believed to occur as follows: 



CeHs-CHCOOH > CeHsCCOOH > CeHsCHCOOH > 



CH3 CH2 CHO 



CeHs-CHjCHO > CeHB-CHaCOOH 



Suggested Pathway of Metabolism of a-Phenylpropionic (Hydratropic) Acid^ 



Although the results on a-phenylpropionic acid indicated a demethyla- 

 tion and the formation of the corresponding straight-chain acid, this com- 

 pound has only one aliphatic |8-carbon. This would automatically preclude 

 the second pathway postulated above, namely, oxidation on the second 

 jff-carbon with the cleavage of a three-carbon fragment which includes the 

 a-methyl group. Kay and Raper^ answered this criticism by experiments 

 with a:-methyl-/3-phenylpropionic acid, C6H5-CH2-CH(CH3) -COOH, and 

 a-methyl-7-phenylbutyric acid, CeHa • CH-, • CH2 • CH(CH3) • COOH. Both 

 of these acids have two j8-aliphatic carbons. When these acids were given 

 in moderate doses to dogs, the end-products were benzoic and phenyl- 

 acetic acid, which are likewise the intermediates after phenylpropionic or 

 phenylbutyric acids are fed. In all cases, these acids were found to be 

 conjugated with glycine or glucuronic acid before being excreted in the 

 urine. When a-methylphenylpropionic acid was fed to cats, a-methyl- 

 cinnamic acid and benzoic acid were present in the urine. 



2C6H5-CH2-CHCOOH > C6H5CH=C-COOH + CeHsCOOH 



CH3 CH3 



a!-Methyl-/3-phenyl- a-Methylcinnaniic Benzoic 



propionic acid acid acid 



The Pathway of Oxidation of Qr-Methyl-/3-Phenylpropionic Acid in Cats* 



These results strongly support the hypothesis that oxidation of a-methyl 

 acids occurs on the /S (non-methyl) -carbon, provided it is an aliphatic 

 carbon. Carter® obtained substantially identical results, and postulated 

 the following general scheme of oxidation of a-methyl-substituted acids : 



C6H8(CH2)xCH2CHCOOH > C6H5(CH2)xCH:CCOOH > 



CH3 CH3 



C6H5-(CH2)xCOCHCOOH > C6H5rCH2)x-COOH 



CH3 

 General Scheme for Oxidation of an a-Methyl-Substituted .\cid® 

 « H. E. Carter, Biol. Symposia, 5, 47-63 (1941). 



