294 VII. ACIDS, AMIDES, ALDEHYDES AND HYDROCARBONS 



However, co-phenyl-substituted acids with groups larger than methyl 

 in the a-position are resistant to oxidation in the animal body. Carter^ 

 reported that both a-ethyl and a-propyl-iS-phenylpropionic acids (CeHs-- 

 CH2-CH(C2H5)-COOH and C6H5-CH2CH(C3H7) -COOH) were excreted 

 unchanged. Likewise, Kuhn and Livada^ noted that a-ethylcinnamic acid 

 (C6H5CH:C(C2H5)-COOH and a-benzylcrotonic acid (CH3-CH:C(CH2-- 

 C6Hb)-C00H) were excreted unchanged by dogs and rabbits. Carter* 

 suggests that, when the a-substituted group is larger than a methyl, steric 

 hindrance prevents enzymatic attack on the carbon chain. 



When a simple a-methyl-substituted acid such as a-methylbutyrate 

 (CH3-CH2-CH(CH3) -COOH) is metabohzed, the mechanism of /3-oxida- 

 tion is presumably still operative. Thus, Coon and Abrahamsen^ are of the 

 opinion that /3-oxidation occurs on the longer chain to produce "acetate" 

 and a three-carbon acid fragment. These results are in accord with the 

 belief that methylbutyrate is an intermediate in isoleucine metabolism, 

 and they accomit for the weakly ketogenic action of this acid as established 

 by Butts et al.^ If the three-carbon acid is propionic, it would also furnish 

 evidence of a source of the glycogen noted after the feeding of isoleucine.^ 



(2) ^-Methyl-Substituted Acids 



/S-Methyl-substituted acids are ordinarily resistant to demethylation. 

 Thus, Kuhn and Livada^ reported that /?-phenylbutyric acid (CeHs-CH- 

 (CH3)-CH2.COOH) is conjugated with glycine or glucuronic acid by rab- 

 bits, and is excreted.^ The fact that some j8-phenylcrotonic acid (CeHs-C- 

 (CH3) : CH • COOH) is present as an excretion product is taken to mean that 

 desaturation, rather than formation of a ;8-keto acid, is the first step in j8- 

 oxidation. Carter^ confirmed the results of Kuhn and Livada.' Carter 

 recognized that the substituted cinnamic acid can originate by the intro- 

 duction of an hydroxyl radicle on the jS-carbon, followed by removal of a 

 molecule of water, as well as by primary desaturation in the a,|S-positions ; 

 however, he favors the second possibility. 



co-Oxidation is sometimes called into play to effect the oxidation of ^- 

 methyl-substituted acids. Thus, Hirohata and collaborators^ reported 

 that, when L-rhodinic acid was administered to dogs, cats, rabbits, or 

 human subjects, it underwent co-oxidation to a large extent, and was ex- 

 creted as dihydro-Hildebrandt acid. Moreover, after the administration 

 of geranic acid to man, as well as after that of tetrahydrogeranic acid, both 



' R. Kuhn and K. Livada, Z. physiol. Chem., 220, 235-246 (1933). 



8 J. S. Butts, H. Blunden, and M. S. Dunn, /. Biol. Chem., 120, 289-295 (1937). 



