PERMEABILITY OF CELLS TO MALONATE 191 



that the intracellular pH^ must fall. This may not only damage the met- 

 abolic systems but wiU tend to reduce the inhibition on succinate dehydro- 

 genase by decreasing the concentration of dicarboxylate anion. 



If one assumes that the HI~ form can also penetrate, the internal con- 

 centration of the active 1= form will not be so strongly dependent on the 

 external pH^, and the inhibition will increase significantly as the pH^ is 

 lowered from 6 to 5, but otherwise the same behavior will be expected. It 

 is usually dif&cult to distinguish between penetration by the Hgl form only 

 and penetration by the HI" form also. Some arguments have arisen on this 

 point, Bonner and Wildman (1946) believing that the HI~ form penetrates 

 and Beevers (1952) holding that only the Hgl penetrates. A Simon-Beevers 

 plot of the data from maize roots (see Chapter 1-14) shows that (Hgl) does 

 not remain constant for 50% inhibition of respiration over the pH range 

 3-6.5, which would indicate a possible contribution from the HI~ form. 

 Actually, it might be better to express the total entry rate of malonate as: 



Entry rate = Phj(H2I)o + Phi-(HI-)o + Pi=(I=)<, (1-5) 



where the P's represent the permeabilities to the various forms of the inhi- 

 bitor. Although Pjj I > Pri- > Pi-^ above pH 4 (HI~) is much greater 

 than (Hoi) so that the contribution of the second term to the total rate may 

 be significant. One would like to know the relative values of the P's for a 

 particular tissue and these could be determined if the entry rate of mal- 

 onate were determined (for example, with labeled malonate) at different 

 pH values. One must also bear in mind that a change of pH could alter 

 the permeability properties of the membrane. 



The only data on the effects of pH on malonate action in animal tissues 

 were obtained on rat ventricle strips by Masuoka et at. (1952). Malonate 

 stimulates the amplitude of hypodynamic strips much more at pH 6.2 

 than at 7.4. This positive inotropic action may be unrelated to the inhi- 

 bition of succinate dehydrogenase, since succinate at pH 6.2 gives essenti- 

 ally the same response, and could depend on the oxidation of malonate 

 (see page 216). Whatever the mechanism, these results indicate that mal- 

 onate penetrates more readily at the lower pH. 



