166 IMMUNO-CATALYSIS 



zyme systems capable of oxidizing several of the fatty acids mentioned 

 above. In evaluating the inhibitions of the tissue enzyme systems it is 

 clear that the inhibition of the oxidation of butyric and crotonic acids 

 by benzoate, cinnamate and phenylpropionate, and relative absence 

 of inhibition of the oxidation of ^-hydroxybutyric acid by these 

 inhibitors indicate their affinity for one enzyme system and not for the 

 other. The inhibition of the specific oxidation of )3-hydroxybutyric acid 

 by the enzyme system used by Green, et al. by iodoacetate, pyruvate, 

 oxalacetate, etc. as well as by the reaction product acetoacetic acid must 

 be attributed to their common affinity for the same enzyme system. 

 Such common affinities for an enzyme are exhibited by substances 

 which are structurally similar to the specific substrates or their reaction 

 products. 



6. Inhibition of Succinoxidase by the Oxidation Product 

 of Succinic Acid, and by Structurally Related Acids 



That acids structurally related to a substrate and to the reaction prod- 

 ucts inhibit the particular enzyme system has been reported by other 

 investigators. Weil-Malhebre (1937) reported that in the presence of 

 an enzyme preparation from fresh ox heart succinic acid consumed 

 (during a two-hour period) 311 fi\ of O2, 1-a-hydroxyglutaric acid, 

 10 fj}, a-glycerophosphate, 29 /xl and d(— )glutamic acid 45 lA; l-(+) 

 glutamic acid and ;8-glycerophosphate were unreactive. In agreement 

 with the earlier observations of Quastel and Wooldridge (1928) he 

 found that malonic acid* inhibited the enzyme completely, whereas 

 maleic acid did not inhibit at all. a-Ketoglutaric acid (M/20) was 

 found to inhibit specifically the succinic dehydrogenase 40-50 per cent. 

 Other keto acids, such as pyruvic or 2-ketogluconic acids or other 

 substances of related constitution, e.g., hydroxyglutaric or glutamic 

 acids, exercised no inhibition. 



Potter and Elvehjem (1937) studied the succinoxidase system of 

 the brain, liver and kidney tissues of rats and chickens. The inhibitory 



^That malonic acid is a biological metabolite has been demonstrated by Raistrick 

 (1938). It is a component of, and is liberated by alkaline hydrolysis of a high molec- 

 ular weight polysaccharide which is produced from glucose by a strain of Penicillium 

 luteum. Vennesland and Evans (1944) reported that the oxidation by tissue of 

 oxalacetic acid, a derivative of succinate, yielded malonate. Malonate, therefore, in- 

 hibits the very enzyme which produces it. 



