208 A SYMPOSIUM ON RESPIRATORY ENZYMES 



acetic acid from pyruvate and carbon dioxide in pigeon breast 

 muscle does not occur, inasmuch as malonate will completely inhibit 

 pyruvate utilization in the absence of added oxalacetic or other 

 dicarboxylic acids. Under these circumstances the synthesis of 

 muscle alpha-ketoglutarate in a radioactive bicarbonate medium 

 would give rise to radioactive alpha-ketoglutarate only if a process 

 of exchange between intermediates in the reaction (such as oxal- 

 acetate) and the carbonate of the medium took place. If the quantity 

 of radioactivity found in muscle alpha-ketoglutarate is similar in 

 magnitude to that found in the alpha-ketoglutarate synthesized by 

 liver, it would eliminate the necessity for proposing a stoichiometric 

 utilization of carbon dioxide in the process. When this reaction is 

 studied in radioactive bicarbonate medium, the alpha-ketoglutarate 

 formed is devoid of radioactivity. There is apparently no appreciable 

 interchange between the carbon dioxide of the medium and the 

 carboxyl group of oxalacetic acid or other intermediates. A similar 

 negative result was obtained in studies of the equilibrium between 

 pyruvic acid and carbon dioxide in the presence of carboxylase in 

 which radioactive carbon dioxide and pressures as high as 300 

 atmospheres were used. Under these circumstances no interchange 

 of carbon dioxide and the carboxyl of the pyruvate could be demon- 

 strated. In view of these data, it seems most probable that the 

 assimilation of carbon dioxide by minced liver is a true metabolic 

 reaction, although the mechanism is still obscure. 



The most promising line of attack of these problems lies probably 

 in the attempt to isolate or simplify the enzyme systems involved. 

 Recently attention has been directed again (17, 18) to the enzymic 

 formation of acetylmethylcarbinol from pyruvate as a possible step 

 in pyruvate oxidation. This reaction has two features of interest: 

 first, it represents an anaerobic, i.e., non-oxidative, decarboxylation of 

 pyruvate; secondly, it poses again the question of acetaldehyde as an 

 intermediate. It is still too early to determine the relative importance 

 of this reaction in pyruvate metabolism of muscle and other tissues. 

 If it should prove to be of significance, the resulting clarity will 

 undoubtedly be suflBcient compensation for the revision that will 

 have to be made in our current beliefs. 



REFERENCES 



1. Krebs, H. a., and Johnson, W. A., Enzymologia, 4, 148 (1937). 



2. Krebs, H. A., and Eggleston, L. V., Biochem. J., 34, 442 (1940). 



3. Krebs, H. A., Biochem. J., 34, 460 (1940). 



4. Krebs, H. A., Biochem. J., 34, 775 (1940). 



