PYRUVATE METABOLISM 



431 



Table 2-24 

 Inhibition of Yeast Pyruvate Decarboxylase by Analogs" 



Inhibitor 



Structure 



Concen- 

 tration 

 (mM) 



Inhibition 



Relative 

 activity 



Glyoxylate 



o-Nitrophenyl- 

 pyruvate 



Ketomalonate 



/)-Hydroxyphe- 

 nylpyruvate 



Phenylpyruvate 



Chloropyruvate 



2, 3-Butanedione 



O 



II 

 H-C-COO 



i> 



CH, 



O 



II 



c-coo 



o 



II 



ooc-c-coo 



HO 



CHj— C-COO' 



O 



II 



CH,— C-COO 



O 



II 

 CI— CH,— C-COO 



O O 



II II 

 HoC C C CHo 



32 



17 



12 



2.9 



56 



1.0 



0.14 



Oxanilate 



a-Ketoglutarate 



O 



II 

 NH- C-COO' 



OOC-CH,— CH,— C— COO 



27 



31 



24 



0.05 



0.012 



o Pyruvate concentration 4.5 mW and preincubation with inhibitor 15 mln. Relative inhibitory 

 activity calculated from the formula t/(l - i)(I) and roughly would be inversely proportional 

 to Kf for noncompetitive Inhibition. (From Gale, 1961.) 



The inhibition by ketomalonate is more surprising when one considers that 

 oxalate and oxalacetate are inactive. The kinetics of the inhibitions pro- 

 duced by the five most potent substances were studied in greater detail 

 and a typical noncompetitive mechanism was established. However, pre- 

 sence of the substrate prevents development of the inhibitions, suggesting 

 that the inhibitors combine at the substrate site. These results indicate an 

 irreversible or pseudoirreversible type of inhibition, and it was indeed de- 

 monstrated that the inhibitions are all progressive with time. Phenylpy- 

 ruvate is the only inhibitor whose effects are even partially reversible by 



