INTRACELLULAR EQUILIBRIA AND SECONDARY EFFECTS 457 



of unstable catalysts kept in existence by the occurrence of reactions which 

 they catalyze. The equilibria here are clearly different from the statically 

 balanced systems of physics and chemistry, a distinction emphasized by 

 Dixon (1949), who termed these equilibria "floating." These very complex 

 equilibria of living material include the steady-state systems discussed in 

 Chapter 7, but are dependent on a higher order .of organization. A certain 

 flow of substance and energy must enter the system for maintenance; an 

 additional amount is required for the performance of function or growth. 

 It is this that imposes instability in living material, in the sense that distur- 

 bances in the metabolism, as produced by inhibitors, can undermine the 

 organized material basis for the metabolism. This instability is generally 

 tempered by the plasticity or adaptability of the cellular metabolism, char- 

 acteristics that have been evolved to protect the cell against periods of 

 adverse conditions, such as deficiencies in substrate or oxygen. Since many 

 inhibitors induce states in cells approximating these deficiencies, the same 

 adaptive processes often come into play, and the dynamic equilibria are 

 not so readily disrupted as might be expected. Nevertheless, once the 

 capacity of the cell to adapt has been exceeded by the metabolic distur- 

 bance, there will be a progressive disintegration of the complex equilibria 

 and eventual dissolution of the structural basis of life. 



Let us consider briefly a very simple illustration of this sort of equilibrium 

 and the effect of inhibitors upon it. Many oxidations require coenzymes 

 that are synthesized in reactions utilizing ATP, which in turn is generated 

 by the oxidations. When an inhibitor depresses the oxidative reaction, 



less ATP will be formed, and consequently less CoE will be available, this 

 further decreasing the oxidative rate; under certain conditions this may pro- 

 ceed until the entire system ceases to function. An inhibitor acting on any 

 other reaction in this equilibrium would have the same end result. Much 

 of the damage to cells resulting from exposure to inhibitors probably results 

 from phenomena of this nature. The instability of mitochondria to anoxia, 

 lack of substrate, or inhibition may be due in part to loss of coenzymes or 

 other metabolically important factors. 



Cells and tissue vary a great deal in their resistance to such disturbances. 

 Anoxia or lack of glucose produces differential damage to cells of the cen- 

 tral nervous system, some surviving for hours and others only for a few 

 minutes (van Liere, 1942), and it is well known that anoxia can induce 

 differential damage to cells lying in the metabolic gradients of the embryo 



