56 1. MALONATE 



Table Ml 



Effects of Endogenous Respikation on Calculations of Malonate Inhibition 

 OF Succinate Oxidation " 



° The true inhibition of succinate oxidation is given in the bottom row, and is to 

 be compared to the figures in the row immediately above where the correction for the 

 endogenous ejRFect has not been made. The concentrations were: pigeon muscle — suc- 

 cinate 1 vaM and malonate 10 iwM (Stare and Baumann, 1939); rat kidney — suc- 

 cinate 20 n\M and malonate 20 mM (Fawaz and Fawaz, 1954); rat liver — succinate 

 10 n\M and malonate 20 mM (Edson 1936); Euglena — succinate 10 mM and malonate 

 10 ml/ (Danforth, 1953). 



HOOC — R — COOH — penetrated, succinate would enter cells somewhat 

 better than malonate, but, at least at pH's above 7, it seems unlikely 

 that this is the situation. Also, the entrance of enough of the undissociated 

 caid to be effective would presumably decrease the intracellular pH signi- 

 ficantly (see Chaper 1-14). Besides, some of these experiments in which 

 malonate was inactive were done at low pH's (3.4 to 5.5). A question that 

 must be considered is whether succinate oxidation is always entirely intra- 

 cellular. It is possible that succinate oxidase occurs both in the mitochondria 

 and in the plasma membrane. In many cases, malonate has little or no effect 

 on tissue metabolism or function at concentrations capable of inhibiting 

 the oxidation of added succinate completely. This is well seen in rat ven- 

 tricle slices (Webb et al, 1949) where the succinate may be oxidized at 

 the cell surface, and it is interesting that in this tissue the potency of mal- 

 onate in vivo and in vitro is the same. However, in most instances, the 

 succinate oxidase seems to be protected in some manner in intact cells. 

 There are several possible factors that could modify the malonate inhi- 



