THE EFFECTS OF EXTRANEOUS AGENTS 

 ON CELL METABOLISM* 



H. A. Krebs 



Medical Research Council Unit for Research in Cell Metabolism, 

 Department of Biochemistry, University of Oxford 



The question has been raised in the preceding contributions 

 whether or not a study of the effects of ionizing radiation on 

 isolated enzyme systems may be expected to solve some of the 

 problems of radiation biology. I would like to offer comments 

 on this question. 



I think it is correct to say that all effects on living cells of 

 radiation, and of extraneous agents generally, are brought 

 about through interference with some chemical substance in 

 the cell. If this substance is an enzyme, the effect of the ex- 

 ternal agent (probably always a reduction of catalytic activity) 

 may cause a significant disturbance in cell metabolism, but 

 this is not necessarily the case. Whether a change of en- 

 zyme activity is of major consequence depends on whether 

 the enzyme concerned plays a role in the rate control of 

 metabolism. 



Pacemaker reactions as vulnerable stages of cell 



metabolism 



The analysis of the circumstances which control the rates of 

 metabolic processes shows that the amount of enzyme present 

 is by no means always the controlling factor. It is true that 



* Abbreviations used: 



DPN diphosphopyridine nucleotide 



DPNH2 reduced diphosphopyridine nucleotide 



ATP, ADP adenosine triphosphate, adenosine diphosphate 



GTP, GDP guanosine triphosphate, guanosine diphosphate 



TPP thiamine pyrophosphate 



P inorganic orthophosphate 



CoA coenzyme A 



92 



