192 1. MALONATE 



In comparing the actions and penetrations of malonate with succinate, 

 or with other dicarboxylate anions, it is necessary to consider that the 

 relative concentrations of the ionic species can be quite different. Thus 

 the HgB form of succinate is at a much higher concentration than the same 

 form of malonate at the same total concentrations (Table 1-3). It is also 

 possible that some cells possess active transport or carrier systems for the 

 substrate dicarboxylate anions, allowing succinate to penetrate more readi- 

 ly than malonate. Permeability in some cases seems to be as specific as 

 are enzyme reactions, and can be quite dependent on the configurations 

 and charge distributions of the transported substances. This could be due 

 to either the structure of the membrane pores or the nature of a carrier. 

 For these reasons one must anticipate striking differences between different 

 tissues with regard to the relative permeabilities to the various ions, and 

 it is particularly important not to apply the results on plants unreservedly 

 to animal tissues or microorganisms. 



GROWTH, DEVELOPMENT, AND DIFFERENTIATION 



The responses of growth, cleavage, and histogenesis to inhibitors are 

 interesting because they often demonstrate the nature of the metabolic 

 basis for these important biological processes. The results may also have 

 bearing on the possible use of the inhibitors for the selective depression 

 of the growth of organisms or abnormal cells which are detrimental to the 

 host. These processes all require energy from the metabolism so that any 

 reduction of either the exergonic reactions or their coupled phosphoryla- 

 tions would be expected to interfere in some manner. In addition, more 

 specific effects may occasionally be observed. The selective inhibition of 

 the growth of certain cells can result from different rates of growth of the 

 cells involved, or from differences in the metabolic requirements for growth. 

 It is generally true that rapidly proliferating cells are more readily affected 

 by inhibitors than are the same or other cells growing or multiplying at 

 slower rates. It has also been demonstrated that various types of cells may 

 utilize different enzymes or metabolic pathways to support proliferation. 

 With respect to malonate, one might anticipate that cells whose growth 

 is in one way or another significantly dependent on the cycle would be 

 inhibited more than cells not requiring the operation of the cycle. However, 

 other factors, such as the degree of penetration of the malonate or the 

 susceptibility of the succinate dehydrogenases to malonate, may be im- 

 portant. 



Virus Multiplication 



Malonate is able in some instances to suppress the intracellular formation 

 of virus without permanently damaging the host cells. The results obtained 



