EFFECTS OF THE DIELECTRIC CONSTANT 799 



system is in a steady state, the over-all rate is determined by reaction 1; 

 if it leaves the steady state it is determined only by reaction 2. The transi- 

 tion from a steady state to a non steady one may be sudden, particularly 

 when some factor limits the rise in the concentration of the intermediate B. 

 Whether the system will or will not pass out of a steady state following a 

 specified rise in the temperature will depend for one thing on how close 

 the initial concentration of B is to the maximal possible concentration. 

 It will also, of course, depend on the difference in the enthalpies of 

 activation for the breakdown of the ES complexes of each step. The 

 addition of an inhibitor to such a system could easily alter the fi value 

 from that for one reaction to that for the other. Also it would be predicted 

 that if a critical temperature is observed in the range studied, an inhibitor 

 would shift this critical temperature down if the inhibition is exerted pri- 

 marily on the second reaction and up if the first reaction is depressed to a 

 relatively greater extent. 



A final word of warning must be spoken for the interpretation of thermal 

 studies on cellular systems. If the rate measured is related solely to a single 

 enzyme or multienzyme process, the effects of temperature on inhibition or 

 the effects of inhibition on temperature characteristics may be attributed 

 directly to these processes. However, if what is measured is a composite 

 rate, the interpretation becomes more uncertain. If ther6 is an appreciable 

 endogenous component or an inhibitor-resistant fraction, the // values will 

 depend also on these processes and changes in // following inhibition may 

 be complex. Furthermore, in work with living cells one cannot always 

 assume a constancy of enzyme concentration because the processes of en- 

 zyme synthesis and inactivation may be modified by inhibitors and changes 

 in the temperature. 



EFFECTS OF THE DIELECTRIC CONSTANT 



The magnitude of the interactions between molecules frequently depends 

 on the dielectric constant of the medium separating and surrounding the 

 molecules. The role of the dielectric constant in various ionic and dipolar 

 interactions has been described in Chapter 6. It is now necessary to inquire 

 into the effects of changes in the dielectric constant on enzyme rates and 

 inhibitions. Inasmuch as the binding of substances to the active sites of 

 enzymes is involved in both enzyme activity and in most inhibitions, it is 

 reasonable to expect that useful information of events on the molecular 

 level might be obtained from experiments in which the dielectric constant 

 is varied. An extensive literature on the effects of the dielectric constant 

 on nonenzyme reactions is available but actually only a small amount of 

 work on enzymes has been reported. However, it is likely that dielectric 

 variation will come to be an important procedure in the investigation of 



