300 VII. ACIDS, AMIDES, ALDEHYDES AND HYDROCARBONS 



and isobutyrate in rumen contents ; it is believed that these probably arise 

 from the bacterial degradation of isoleucine, leucine, and valine. 



Grafflin and Green^^ reported that isocaproic acid ((CH3)2:CH-CH2-- 

 CH2 • COOH) can be oxidized by a kidney enzyme system which contains, 

 in addition, ATP (or adenosine monophosphate), Mg++, and inorganic 

 phosphate. Atchley,^^ likewise making use of the kidney enzyme system, 

 proved that the intermediate in the oxidation of isocaproic acid was iso- 

 butyric acid, as would be expected from the jS-oxidation theory. Isobutyric 

 acid was isolated from the reaction mixture by the use of the counter- 

 current distribution, and was identified. The course of this reaction is 

 indicated below: 



CHav CHsv 



:CH-CH2-CH2-COOH > ;CH-COOH 



Isocaproic acid Isobutyric acid 



The Oxidation of Isocaproic Acid by a Kidney Fatty Acid Oxidizing System''^ 



When isobutyric acid was oxidized by the kidney fatty acid oxidizing 

 system, propionic acid was identified as one of the end-products, by isola- 

 tion with counter-current distribution. Atchley^* pictured the possible 

 pathway of breakdown of isobutyric acid as follows : 



CH3\ +'AO. HOCH2 -HOH CH2V 



:CH-COOH > CHCOOH , ^C-COOH 



Cn/ CH3 +HOH CH3/ 



(I) (11) 



1AO2 HCOv '/2O2 

 > ;CHCOOH > COo + CH3CH2CHO > CH3-CH2COOH 



(III) (IV) (V) 



The Postulated Pathway of Oxidation of Isobutyric Acid (I) through /3-Hydroxyiso- 

 butyric Acid (II), Methyhiialonic Semialdehyde (III), Propionaldehyde (IV) to Pro- 

 pionic Acid (V)^* 



Since propionic acid is quantitatively transformed to glucose, this path- 

 way is in agreement with the finding of Ringer, Frankel, and Jonas-^ that 

 isobutyric acid gives rise to glucose and that isobutyl alcohol yields an 

 amomit of glucose corresponding to the conversion of three of its carbons 

 when it is given to a phlorhizinized dog. The ketogenic activity of 

 branched-chain fatty acids has been discussed earlier (see page 130). 



" A. L. Grafflin and D. E. Green, J. Biol. Chem., 176, 95-115 (1948). 



28 W. A. Atchley, J. Biol. Chem., 176, 123-131 (1948). 



29 A. I. Ringer, E. M. Frankel, and L. Jonas, J. Biol. Chem., I4, 525-538 (1913). 



