Rate-limiting Factors in Cell Respiration 9 



may be looked upon as a structural analogue of a-oxoglutarate, 

 specifically inhibits the removal of a-oxoglutarate. It also 

 inhibits pyruvate removal and oxygen consumption when 

 pyruvate is the only added substrate (Table III), but when 



Table III 



Effect of parapyruvate on oxidative metabolism of pigeon 

 breast muscle homogenate 



The data refer to 8 ml. suspension ; 10 per cent tissue ; 20° ; 1 hr. 



both pyruvate and fumarate are added parapyruvate no 

 longer inhibits oxygen consumption and pyruvate removal. It 

 greatly stimulates the removal of fumarate and the data on 

 the changes of metabolites make it clear that those sections of 

 the tricarboxylic acid cycle which operate in the presence of 

 this inhibitor — the stages between fumarate and a-oxoglutar- 

 ate — proceed more rapidly and thus compensate for the loss 

 of the steps between a-oxoglutarate and fumarate. 



In this introductory talk I must limit myself to giving a few 

 examples of the study of the regulation of reaction rates. The 

 fundamental principle involved in these examples is, I think, 

 control by feedback. This differs basically from the mechan- 

 isms which operate in hormonal control. Hormones usually 

 (if not always) act through direct effects on an enzyme, either 



