306 VII. ACIDS, AMIDES, ALDEHYDES AND HYDROCARBONS 



dicarboxylic acids, succinic, fumaric, malic, and oxaloacetic, and pyruvic 

 acid, had a powerful catalytic influence in increasing oxygen uptake and 

 carbon dioxide production by muscles and by other tissues. It was recog- 

 nized that the succinate -^ fumarate reaction is inhibited by malonate,^^ 

 while the fumarate -^ malate conversion is blocked by arsenite. 



Martins'*^ was the first to demonstrate that citric, isocitric, and cis- 

 aconitic acids are readily interconvertible in the tissues, while Martins 

 and Knoop'*'' and Martius alone^^ observed that citric acid can be trans- 

 formed into a-ketoglutaric acid. Ochoa and Weisz-Tabori^^ discovered 

 the enzyme, oxalosuccinic carboxylase, which is capable of causing the 

 decarboxylation of oxalosuccinic acid, with the resultant formation of a- 

 ketoglutaric acid. This enzyme also catalyzes the reverse reaction by 

 causing the incorporation of CO2 into a-ketoglutaric acid to form oxalosuc- 

 cinic acid. Apparently the enzyme is widely distributed in tissues. 



Another key reaction is the conversion of a-ketoglutaric acid to succinic 

 acid.*" This is accomplished by the intermediation of the a-ketoglutaric 

 acid dehydrogenase system. According to Ochoa,* ^ both ATP and the 

 cytochrome system are required for the completion of this reaction. The 

 details of the mechanism of condensation of oxaloacetic acid and of acetic 

 acid to yield citric acid have been recorded by Stern and Ochoa.*-*' 



(b) The Role of Dicarboxylic Acids as Intermediary Products in Fatty Acid 

 Oxidation. Omega-oxidation, with the resultant formation of a dicar- 

 boxylic acid, is believed to afford an alternate pathway for the oxidation 

 of fatty acids. Verkade and co-workers** reported that the fatty acids of 

 medium length, when fed to man as their triglycerides, were in part ex- 

 creted as dicarboxylic acids of the same chain length, or as dicarboxylic 

 acids with two or four fewer carbons than the original acids. This reac- 

 tion occurs principally with C9, Cio, and Cu acids, but Cg and C12 also 

 exhibit a limited amount of this type of oxidation. This course of oxida- 

 tion for capric acid is pictured on the following page : 



« C. Martius, Z. physiol. Chem., 257, 29-42 dQSS). 



^' C. Martius and F. Knoop, Z. physiol. Chem., £46, I-II (1937). 



« C. Martius, Z. physiol. Chem., ^47, 104-110 (19.37). 



« S. Ochoa and E. Weisz-Tabori, /. Biol. Chem., 15!), 245-246 (1945); 174, 123-132 

 (1948). 



so H. A. Krebs and W. A. Johnson, Biochem. J., 31, G45-660 (1937). 



61 S. Ochoa, /. Biol. Chem., 155, 87-100 (1944). 



" J. R. Stern and S. Ochoa, J. Biol. Chem., 179, 491-492 (1949). 



" J. R. Stern and S. Ochoa, Federation Proc, 9, 234-235 (1950). 



" P. E. Verkade, M. Elzas, J. van der Lee, H. H. de Wolff, A. Verkade-Sandbergen, 

 and D. Van der Sande, Proc. koninkl. Akad. Wetenschap., Amsterdam, 35, Afdeel. Natu- 

 urk., 251-266 (1932). 



