ENZYMES OTHER THAN SUCCINATE DEHYDROGENASE 



67 



in rat tissue homogenates by Pardee and Potter (1949). The formation 

 of citrate here probably involves decarboxylation of some of the oxal- 

 acetate to pyruvate, with subsequent condensation to enter the cycle. Al- 

 though a single enzyme was not studied, it is possible that the utilization 

 of oxalacetate was limited by the decarboxylase. This reaction is activated 

 by low concentrations of Mg++ and inhibited by higher concentrations 

 (upper curve in Fig. 1-10). It is clear that the inhibition by malonate de- 



( Mg* • ). 



30 

 mM 



Fig. 1-10. Utilization of oxalacetate by a rat 



kidney homogenate at diflferent concentrations 



of Mg++, with and without malonate. (From 



Pardee and Potter, 1949). 



creases as the Mg"*"*" concentration is raised (lower curve). This was interpret- 

 ed to mean that the inhibition is mainly due to depletion of Mg++. Some 

 arguments may be brought against this interpretation. Table 1-13 gives 

 my calculations of the concentrations of free Mg^^, free malonate, and the 

 complex at the different levels of total Mg++ used in the experiment shown 

 in Fig. 1-10. It is seen that the malonate at 10 mM does indeed reduce the 

 free Mg++, but in the higher range of Mg++ concentrations this should in- 

 crease the activity rather than decrease it, because in this range Mg"'"+ is 

 somewhat inhibitory. Pardee and Potter did not consider the reduction in 

 free malonate concentration, which is very marked as shown in Table 1-13. 

 This could well acount for the decrease in the inhibition from 47% at zero 

 Mg++ concentration to 12% at 30 roM Mg++. One might speculate that the 

 reduction in rate at high Mg++ concentrations could be due to the complexing 

 of oxalacetate so that it is unable to react with the enzyme. The question 

 of the mechanism of the malonate inhibition is thus not settled. It was 

 claimed that the inhibition is not typically competitive because increase 

 in the oxalacetate concentration actually increases the inhibition somewhat, 



