10 Sir Hans Krebs 



activating or inhibiting it. In contrast, feedback systems are 

 arrangements in which the rate does not depend on the 

 potential activity of the enzymes, but on environmental 

 factors. The controlled process, as it progresses, creates 

 conditions unfavourable for further progress and thereby 

 causes the rate to slow down. This slowing down, in turn, 

 creates more favourable conditions and thus speeds up the 

 process. This is obvious for the rate control of the total 

 energy supply. Energy expenditure means a conversion of 

 ATP to ADP and phosphate. As each of these products is a 

 reactant in the aerobic and anaerobic energy supply, their 

 formation can accelerate the reactions which lead to their 

 removal. In other words, ADP and phosphate provide the 

 stimulus (or "signal", to use a term of feedback engineering) 

 for the acceleration of the energy-supplying reactions. 



Competitive mechanisms in which the pyridine nucleotides 

 and other cofactors are the key substances may also be looked 

 upon as feedback systems. When two substrates compete for 

 one common intermediary catalyst each by its presence 

 creates unfavourable conditions for the reaction of the other 

 substrate. As one of the substrates disappears the second is 

 automatically "fed" to the catalyst so that approximate 

 constancy of catalytic activity is secured. Whether all " primi- 

 tive " control mechanisms can be classified as feedback systems 

 remains to be seen. This is one of the many questions which I 

 hope this symposium will help to illuminate. 



REFERENCES 



Aldridge, W. N. (1957). Biochem. J., 67, 423. 



Chance, B. (1956). Proc. Ill int. Congr. Biochem., p. 300. New York: 



Academic Press. 

 Krebs, H. A. (1956). Dtsch. med. Wschr., 81, 4. 

 Krebs, H. A. (1957). Endeavour, 16, 63, 125-132. 

 Lardy, H. A., and Wellman, H. (1952). J. biol. Chem., 195, 215. 

 LooMis, W. F., and Lipmann, F. (1948). J. biol. Chem., 173, 807. 

 Montgomery, C. M., and Webb, J. L. (1956). J. biol. Chem., 221, 359. 

 Tyler, D. B. (1949). J. biol. Chem., 184, 711. 



