INHIBITION OF SUCCINATE DEHYDROGENASE 



45 



extended form shown in the figure, whereas maleate might not fit because 

 of its nonlinear structure. Acetylene-dicarboxylate would be expected to in- 

 hibit to some extent because of its linearity. Such a model would also ex- 

 plain why small alkyl groups added to succinate do not completely abolish 

 the binding. It may also be mentioned that this type of configuration would 

 allow the flavin and iron components of the dehydrogenase to be in posi- 

 tions close to the — CH2CH2 — group and thus able to participate in the 

 removal of the hydrogen atoms. 



Succinate 



Fig. 1-8. Representations of the binding 

 of malonate and succinate at the active 

 site of succinate dehydrogenase, indicat- 

 ing the steric barriers possibly surround- 

 ing the region of the two cationic sites. 

 The actual situation must be visualized 

 in three dimensions. 



Activation of Succinate Dehydrogenase by Malonate 



Preparations of beef heart succinate oxidase obtained using borate buf- 

 fer are not fully active but may be activated by the addition of phosphate. 

 This interesting discovery by Kearney (1957, 1958) may have important 

 bearings on the understanding of the active center of this enzyme, especially 

 as she later found that succinate, fumarate, and malonate also activate, 

 and indeed are much more potent than phosphate (see accompanying 

 tabulation). Once the enzyme has been activated, the activator can be 

 removed without loss of the activity; in fact, malonate must be dialyzed 

 away if the full activity of the enzyme is to be measured. The activation 

 constants are quite different from the Michaelis or inhibitor constants for 

 these substances. It would appear that malonate binds more tightly to the 

 less active form of the enzyme. Kearney favors the view that these activa- 



