ANTIBODY AS A SPECIFIC ENZYME INHIBITOR 165 



5. Inhibition of the Oxidation of /^-Hydroxybutyric Acid 

 by Its Reaction Product Acetoacetic Acid and Related 



Acids 



Jowett and Quastel (1935) found that fatty acids are oxidized at 

 considerable rates by slices of liver in vitro and give as one of their 

 oxidation products acetoacetic acid, as in the body. Jowett and Quastel 

 (1935) studied the rate of acetoacetic acid production from butyric, 

 crotonic and ^-hydroxybutyric acid under various conditions. On the 

 basis of the results obtained they proposed a mechanism of the oxida- 

 tion of these acids to acetoacetic acid as follows: 



Crotonate 



>iAcetoacetate±^^-hydroxybutyrate 



Butyrate ^ 



They found that 0.00 IM benzoate, cinnamate and phenylpropionate 

 strongly inhibit the oxidation of butyric and crotonic acids to acetoacetic 

 acid. Cinnamate and propionate inhibit oxidation of /?-hydroxybutyric 

 acid to a much smaller extent than the oxidation of butyric and crotonic 

 acids. 



Green, Dewan and Leloir (1937) studied the nature of the enzyme 

 system responsible for the oxidation of j8-hydroxybutyric acid to ace- 

 toacetic acid. The dehydrogenase system was prepared from heart 

 muscle, and coenzyme I was found to be an indispensable component 

 of the system. This system specifically catalyzed the oxidation of 

 l-/?-hydroxybutyrate to acetoacetate. They also showed that the change 

 from y8-hydroxybutyrate to acetoacetate is reversible. The highly specific 

 nature of the dehydrogenase system was evidenced by the fact that it 

 did not catalyze the oxidation of iS-hydroxypropionic, a-hydroxybutyric, 

 crotonic, y-hydroxybutyric, butyric and acetic acids. 



The above specific dehydrogenase system was inhibited by 0.03 M 

 iodoacetate, pyruvate and oxalacetate 56, 48 and 71 per cent, re- 

 spectively. Under identical conditions the inhibition by 0.012 M of 

 the reaction product, acetoacetic acid, was 55 per cent. 



Green et at., as cited above, appear to have shown that the tissue 

 slices used by Quastel and his associates represent a mixture of en- 



