INHIBITION OF SUCCINATE DEHYDKOGENASE 49 



The succinate dehydrogenase of Micrococcus lactilyticus behaves quite 

 differently and is poorly inhibited by malonate, a ratio of (malonate)/(fu- 

 marate) = 20 being required for 29% inhibition (Peck et al, 1957). It might 

 be thought that this enzyme is not succinate dehydrogenase, but another 

 enzyme that could be called " fumarate reductase," especially as fumarate 

 is reduced at a faster rate than succinate is oxidized, in contrast to the 

 mammalian enzymes. However, it has been conclusively demonstrated 

 it is not a separate enzyme and that the failure of malonate to inhibit 

 is to be attributed to a very high affinity for fumarate coupled with a rela- 

 tively low affinity for malonate (Warringa et al., 1958). The configuration 

 of the active center of the bacterial enzyme must differ from that of the 

 mammalian enzymes. This may also explain the "fumarate reductases" 

 obtained from yeast (Fischer and Eysenbach, 1937; Kovac, 1960) which are 

 rather insensitive to malonate. 



Variations of Malonate Inhibition of Succinate Dehydrogenases 

 from Different Tissues and Species 



The comparative biochemistry of enzyme inhibition is in its infancy and 

 accurate comparison of results is usually impossible due to the different 

 conditions under w^hich the inhibitions w^ere studied. Examination of Table 

 1-6 with a view to establishing phylogenetic relationships is made difficult 

 by the different types of preparation and assay procedure used. A correla- 

 tion graph, made by plotting inhibitions against (I)/(S) ratios, shows a very 

 marked scatter of the points. For example, at an (I)/(S) ratio of 0.1. the 

 inhibitions range from 10% to 100%. This variation cannot all be due to 

 the differences in technique. All of those cases in which the malonate inhibi- 

 tion is significantly below the mean turn out to be in the bacteria, inverte- 

 brates, or plants. However, this is not a strict correlation because some of the 

 potent inhibitions have been found in such organisms {e.g., Azotobacter, E. 

 colt, and Trypanosoma). The possibility of a relationship between succinate 

 dehydrogenase type in the bacteria and the oxygen requirements for growth 

 has been proposed. The enzyme from the obligate anaerobe Micrococcus 

 lactilyticus has low affinities for succinate and malonate, as discussed in the 

 previous section, whereas the enzyme from the facultative anaerobe, 

 Propionibacterium pentosaceum is intermediate in properties between Mi- 

 crococcus and the aerobic mammalian tissues (Singer and Lara, 1958). Cer- 

 tainly many invertebrate and plant tissues can withstand anaerobiosis 

 better than mammalian tissues, but at the present state of our knowledge 

 such a correlation is dangerous to make. 



Comparisons of the malonate inhibitions of succinate dehydrogenases 

 from different tissues have been reported in a few cases. The epithelium 

 and muscle of guinea pig seminal vesicle were separated and the inhibitions 

 by malonate at four different concentrations were similar (Levey and Szego, 



