Discussion 11 



DISCUSSION 



Hinshelwood: An interesting example of the type of change in the 

 limiting process which Sir Hans has been discussing, is found in the 

 oxidation of various carbon substrates by Aerohacter. Many of them 

 need to undergo a good deal of adaptation before Aerohacter will grow 

 on them as sources of carbon at its optimum rate. During the process of 

 adaptation to a given substrate, or in the comparison of different sub- 

 strates to which the bacteria are poorly adapted, there is found a good, 

 and more or less linear, correlation between the growth rate and the 

 oxygen consumption (without growth) in the presence of the substrate. 

 However, for the whole group of substrates the same optimum degree of 

 oxygen uptake is reached eventually. It becomes the same and con- 

 stant, when the cells are fully adapted. Therefore, when they are badly 

 adapted the limiting step is the initial oxidation of the substrate. They 

 reach the constant optimum when the limiting factor has changed, the 

 oxidation rates, which were all different, now being the same for the 

 whole series. 



Krehs : Yes, that would be an example of a change of limiting factors 

 under different conditions. 



Magasanik: Sir Cyril, does not that actually involve the formation 

 of new enzymes? In other words, adaptation here means the increase 

 in enzyme levels which is then responsible for the greater oxygen 

 uptake. 



Hinshelwood: When the requisite dehydrogenase is developed to the 

 maximum extent that the bacteria are capable of, then in all the dif- 

 ferent cases there is the same constant optimum. This shows that the 

 limiting factor is no longer the rate of substrate oxidation but something 

 else, perhaps the rate of reoxidation of the reduced carriers. 



Potter : Sir Hans, in the beginning it sounded as if you made a general- 

 ization that most control mechanisms, or most regulations, operated 

 through changes in the reaction rate as if it were only in terms of enzyme 

 activity. To clarify that point, I am sure you would agree that there 

 are many situations in which changes in enzyme amount are very 

 important. 



Krehs: I referred to heart muscle or a striated muscle where the 

 amount of enzyme would not be varied when the rate of reaction 

 changes. Of course, there are conditions e.g. in the adapting micro- 

 organism, where the amount of enzyme becomes the limiting factor. 



Chance : It would be important to define what we mean by velocity of 

 enzyme reactions, and to state how the concentration of enzyme 

 affects the velocity of enzyme reactions. There is a difference between 

 velocities and velocity constants. The velocity constant is the rate of 

 breakdown of the saturated intermediate, but the velocity or the 

 amount of substrate decomposed per unit time will be the product of 

 this velocity constant and the amount of enzyme. The velocity constant 

 with which the intermediate breaks down is a constant characteristic 

 of the enzyme — you cannot say that it is a variable for any particular 

 system. 



