EFFECTS OF TEMPERATURE: CELLULAR SYSTEMS 795 



cal temperatures). These breaks have been interpreted as indicating a tran- 

 sition between two different limiting reactions with different temperature 

 characteristics. These matters have been much discussed (Burton, 1936, 

 1939; Sizer, 1943; Morales, 1947; Stearn, 1949; Kavanau, 1950) but gen- 

 eral agreement has not been reached. 



Dixon and Webb (1958, p. 163) have suggested six explanations for the 

 discontinuities observed in the log v — IjT plots for enzyme reactions. 



{a) Phase change in the solvent (as the freezing of water at 0°). 



(6) Two parallel reactions with quite different temperature coefficients 

 so that different reactions are dominant in different temperature ranges 

 (predicting higher // values at the higher temperatures which is usually 

 not the case). 



(c) Two successive reactions with different temperature coefficients so 

 that different reactions are limiting in different temperature ranges. 



{(I) Enzyme can exist in active and inactive forms with a high tempera- 

 ture coefficient for the transformation reaction between them. 



(e) Enzyme may be reversibly inactivated, either spontaneously or by 

 some substance in the medium. 



(/) Discontinuity affecting the forward reaction only. 



Koshland (1959) applied these mechanisms to the myosin ATPase system 

 and concluded that a flexibility in the active center might be involved, 

 this being a variation of explanation {d) above. It may be mentioned that 

 in cellular systems additional explanations may be imagined for the crit- 

 ical temperatures observed. 



We may now inquire as to how an inhibitor could alter // for an enzyme 

 reaction. Inasmuch as // is closely related to the enthalpy of activation 

 for the breakdown of the ES complex, an inhibitor that alters J/^* will 

 probably change //. It would be expected that competitive inhibitors would 

 not produce any change in // since they do not interfere with the breakdown 

 of the ES complex but only with its formation. Noncompetititive inhibitors 

 on the other hand modify ic.^ and hence could change //. Coupling inhibitors 

 and inhibitors binding with the substrate or coenzymes may or may not 

 effect //, depending on the nature or activity of the complexes formed. In 

 addition, we have seen above that // can also depend on iiC,„ and the enthal- 

 pies and entropies of the ES complex formation, and under certain circum- 

 stances these can be altered by inhibitors. There are very few quantitative 

 studies on the effects of inhibitors on enzyme /.i values, but it would appear 

 that this might be a reasonably useful approach in the determination 

 of the interactions of substances on the enzyme surface. 



The inhibition of horse serum cholinesterase by quinine is affected by 

 the temperature in an interesting manner (Robert et al., 1951). The inhi- 



