202 



UNITY AND DIV^ERSITY IN BIOCHEMISTRY 



This particular form of the system of dicarboxylic acids had to be 

 abandoned when Krebs showed that a-ketoglutarate and citrate, in addition 

 to succinate, fumarate, malate and oxaloacetate, also re-establish the 

 respiration of a muscle pulp. The case of a-ketoglutaric acid, in the scheme 

 of Szent-Gyorgyi, did not present an insurmountable difficulty since the 

 oxidative decarboxylation of a-ketoglutarate yields succinic acid. 



COOH 

 I 



CH2 



I 

 CO 



COOH 



a-ketoglutaric acid 



+ H,0 



2H 



COOH 



I 



CHo 



CH, 



■f CO2 



COOH 



succinic acid 



Apparently the entry of citric acid into the scheme can be explained by 

 the conversion of citrate into a-ketoglutarate under the action of a citric 

 dehydrogenase. But an examination of the formulas of citric acid and 

 a-ketoglutaric acid shows that citric dehydrogenase cannot convert the first 

 into the second in one step. 



COOH 



CH. 



C(OH)COOH 



I 



CH2 



COOH 



citric acid 



COOH 



CHo 



I 

 CH2 



CO 



COOH 



a-ketoglutaric acid 



It was then that the very important discovery of aconitase (Martius and 

 Knoop) was announced and it was demonstrated that the so-called citric 

 dehydrogenase was in fact a mixture of aconitase, isocitric dehydrogenase, 

 and oxalosuccinic decarboxylase. This multi-enzyme system explained the 

 passage of citrate to succinate. 



