50 1. MALONATE 



1955). However, the inhibitions of epithelial dehydrogenase appear to be 

 about 5% higher than for the muscle enzyme, although this may not be 

 statistically significant. Malonate was found to inhibit Hepatoma 134 

 tumor succinate dehydrogenase more than the enzyme from normal mouse 

 liver (Fishgold, 1957) over a range of five malonate concentrations; for 

 example, 0.21 mM malonate inhibited the liver enzyme 42% and the he- 

 patoma enzyme 76% at a succinate concentration of 1 vaM. Killer and 

 sensitive stocks of paramecia may have succinate dehydrogenases with 

 different sensitivities to malonate, but it is difficult to draw conclusions 

 from the data published (Simonsen and van Wagtendonk, 1956). The Og 

 uptake of homogenates of the two strains was increased to different de- 

 grees by 50 mM succinate and malonate inhibited both quite well (see 

 accompanying tabulation). The authors concluded that the enzyme from 

 the killer strain, is inhibited more, based on absolute reduction, but actually 



Increase in Oj uptake from succinate 



Sensitive strain Killer strain 



Control 1.4 14.0 



With malonate 80 mM 0.2 3.8 



% Inhibition 86 73 



the enzyme from the sensitive strain seems to be inhibited as w^ell. Our 

 work with succinate dehydrogenase from various rat tissues (Table 1-6) 

 indicates no significant difference in susceptibility to malonate. 



INHIBITION OF SUCCINATE OXIDATION 

 IN CELLULAR PREPARATIONS 



Attention will now be turned to the inhibition of the succinate oxidase 

 system when it is located in the normal cellular structure and succinate is 

 added exogenously to the preparations. When succinate is added to most 

 cell suspensions, minces, or slices, there is an increase in the O2 uptake, 

 and this response is inhibited to varying degrees by malonate (Table 1-10). 

 It is particularly important in cellular preparations to take account of the 

 endogenous respiration and the effect of malonate on it (see Chapter 1-9). 

 In many studies this has not been done and this is one factor that makes 

 it difficult to compare accurately the malonate inhibitions m vitro and in 

 vivo. Since the endogenous respiration is generally inhibited less than 

 succinate oxidation by malonate, failure to correct for endogenous respi- 

 ration usually leads to low values for the inhibition. This is illustrated in 



