8 Sir Hans Krebs 



between a substrate and DPN is the presence of another sub- 

 strate. Under physiological conditions it is usual that a 

 variety of different substrates derived from either carbo- 

 hydrate, or protein or fat, is available. When a mixture. of 

 substrates is offered they do not all undergo oxidation at the 

 same time, but one after the other, in such a fashion that the 

 energy supply remains steady, and independent of the 

 quantity of substrates offered. Thus, when a variety of sub- 

 stances are available they compete with each other as fuels. 

 Enzymically this represents in most cases a competition for 

 DPN, and in special cases for other common cof actors. We 

 can test, by direct experiments offering a mixture of sub- 

 strates, which of the substrates wins in the competition and 

 it is also possible to explain in a general way why they win, 

 namely because of a higher reaction rate under the given con- 

 ditions. But the physicochemical properties of the enzyme 

 systems which determine the reaction rate have as yet to be 

 analysed. 



The competition between substrates for DPN may be 

 visualized as follows. DPN is known to be attached to de- 

 hydrogenases as the prosthetic group. If the substrate of the 

 dehydrogenase is available, this prosthetic group will undergo 

 reduction but no further substrate can be attacked until the 

 prosthetic group has been reoxidized by the transfer of 

 electrons to the next stage of the electron transport chain, 

 namely flavoprotein. Thus, if several substrates are present 

 the respective dehydrogenases will be converted to the 

 reduced forms and these are therefore the agents which com- 

 pete for a common electron carrier. 



An example of competition between substrates is the ob- 

 servation that inhibition of dehydrogenases by specific 

 inhibitors does not necessarily change the rate of oxygen 

 consumption of a tissue preparation, because the place of the 

 eliminated substrate can be taken by others. An illustrative 

 case is the effect of parapyruvate on the metabolism of 

 muscle tissue. As Montgomery and Webb (1956) have shown, 

 parapyruvate [COOH.C(OH)(CH3).CH2.CO.COOH], which 



