68 1. MALONATE 



Table 1-13 



Effects of Total Mg++ Concentration on the Concentrations of Free Mg++, 

 Free Malonate, and Ms-Malonate Complex " 



" Conditions as in Fig. 1-10 from the work of Pardee and Potter (1949). The total 

 malonate concentration is 10 mM in all cases. The values were calculated from Eq. 

 1-3 using 9.77 X 10^^ M for the dissociation constant of the Mg-malonate complex. 



although no figures were given so the magnitude of the effect is unknown. 

 An increase of oxalacetate might reduce the amount of Mg++ bound to 

 malonate and thereby increase the free malonate concentration. It would 

 appear unlikely that the Mg-malonate complex is inhibitory since its con- 

 centration increases with Mg++ concentration (Table 1-13), whereas the 

 inhibition decreases. However, it is evident that malonate inhibits this 

 enzyme system in some manner directly, not only from the above consid- 

 erations but also because of the marked inhibition observed in the absence 

 of Mg++. 



Dialkylfluorophosphatase is activated by Mn++ and its inhibition by 

 malonate was attributed by Mounter and Chanutin (1953) to the chelation 

 of the activator. Since no concentrations of either Mn++ or malonate were 

 given, it is impossible to evaluate the results. However, their data show 

 that malonate inhibits just as well, if not better, in the absence of Mn++ 

 (21% with Mn++ added and 28% without Mn++ at 15 min). These results 

 might better be interpreted as due to removal of free malonate by the 

 Mn++. If Mn-malonate is incubated with the Mn-free enzyme, activity 

 slowly appears, indicating that the Mn++ is transferred from the malonate 

 to the enzyme, which is not surprising since the affinity of the enzyme for 

 the Mn++ is much greater, as shown by the dissociation constants {pK for 

 enzyme-Mn++ complex is 7.7). It would be very surprising under these 

 circumstances if malonate were able to reduce the Mn++ sufficiently to 

 inhibit the enzyme. 



There are several other claims for this mechanism of malonate inhibi- 

 tion but in all cases there is either inadequate evidence or no evidence at 



