56 INFLUENCE OF TEMPERATURE ON BIOLOGICAL SYSTEMS 



some work with ChE and its inhibitors. However, the problem is not one 

 of interest only to entomologists ; for surely we all have something to learn 

 by attempting to extend our temperature studies of this vitally significant 

 system to truly vital situations. 



SUMMARY 



The literature on the response of cholinesterases (ChE's) to temperature 

 change has been reviewed. The available data are discussed under three 

 headings: 1) temperature and rate of hydrolysis, 2} inactivation of ChE by 

 heat and 3) efi^ect of temperature on the rate of reaction with inhibitors. 



The temperature coefficient of ChE-catalzyed hydrolysis of acetyl- 

 choline (ACh) and other substrates is generally small. Qio values from 

 1.3 to 1.5 are usual. With many preparations, activity is directly pro- 

 portional to temperature over the range below 35°C, but some experiments 

 have given results consonant with the Arrhenius formulation. Other dif- 

 ficulties concerned in the calculation and interpretation of the standard 

 thermodynamic constants are outlined ; and it is concluded that with most 

 preparations the temperature response is modified by complicating factors 

 of an unknown nature. 



Heat inactivation of ChE's is rapid at temperatures above 50°C. Fly 

 head preparations are somewhat more sensitive than the ChE's of mam- 

 malian blood. Apparent energies of activation for the denaturation are of 

 the order of 40-60 Cal/mole; however, the reaction fails to follow first- 

 order kinetics over longer exposures, and analysis of the data shows a rapid 

 initial phase and a subsequent slower phase. Both processes appear to be 

 of first order. The reason for the biphasic course of denaturation is not 

 known, although it obviously indicates that more than one reaction is in- 

 volved in the denaturation process. 



The ChE's of mammalian serum are in addition reversibly inhibited at 

 temperatures above 40°C. In contrast, all of the reduction in activity ob- 

 served with fly head ChE is attributable to irreversible denaturation. None 

 of the current hypotheses accounts satisfactorily for all of the anomalies 

 in the temperature response. 



The temperature dependence of the reaction with competitive inhibitors, 

 whether reversible or 'irreversible', is in general similar to the response of 

 the enzyme-substrate system, in so far as the scanty data available permit 

 one to judge. Similar complexities are indicated. Some noncompetitive in- 

 hibitors at low concentrations combine reversibly with the enzyme, in a 

 process that has a small temperature coefficient. These same inhibitors, at 

 high concentrations, denature the enzyme irreversibly. The energy require- 

 ment for such denaturations is of the order of 40-60 Cal/mole, as for de- 

 naturation by heat. 



