EFFECTS OF TEMPEKATURE: CELLULAR SYSTEMS 777 



an unfavorable temperature shift will usually be less able to withstand the 

 additional effects of an inhibitor. This applies not to the direct primary 

 actions of the inhibitor but to the eventual over-all changes upon which the 

 survival of the cell depends. A culture of bacteria whose normal tempera- 

 ture range is near 37° may be very unstable near 47°. A further increase of 

 the temperature to 50° may produce a rapid drop in the cell count. Now, 

 it would be expected that an inhibitor affecting some vital pathway in 

 these cells would be more effective in killing the bacteria at 47° than at 

 37°. Exceptions to this rule would be anticipated, especially at reduced 

 temperatures, because other factors, such as a slower rate of inhibition, 

 would also be important. 



Dependence of Respiratory Inhibition on Tennperature 



The oxygen uptake of most cells is made up of contributions from several 

 different pathways. Endogenous respiration particularly usually involves 

 the oxidation of many substrates, sometimes by the same and sometimes 

 by different electron-transport chains. The utilization of glucose by the 

 Embden-Meyerhof glycolytic pathway and the tricarboxylic acid cycle 

 provides at least six different substrates for oxidation, while the addition 

 of the pentose-phosphate shunt would bring in other oxidations. Almost 

 every type of multienzyme system is operative in normal respiration and, 

 furthermore, operating not in isolation but linked together in various ways. 

 Not only are there pathways for the degradations of the substrates and the 

 oxidation of the intermediates, but there are also the many reactions in- 

 volving phosphate that are closely coupled to the total respiratory system. 

 Then there are fatty acids and amino acids and other substrates being bro- 

 ken down and oxidized by pathways that occasionally are confluent with 

 those of carbohydrate metabolism, or which terminate in common channels. 

 The respiratory mechanism alone may be thought of as a kind of super- 

 multienzyme system, the kinetics of which would be inexpressible by our 

 present formulations. 



The effects of temperature on cellular respiration have been studied 

 for many years and the results have often been interpreted in terms of 

 single enzyme reactions on the basis of the theory of limiting or master 

 reactions. We have noted that this concept has very limited applicability 

 (Chapters 7 and 9) and when applied to something as complex as respira- 

 tion, one is justified in maintaining a critical attitude. It has been demons- 

 trated many times by Britton Chance (e.g. Chance and Hess, 1959) that 

 there are multii)le controls of respiration and that under various conditions 

 the rates are limited by different reactions, even in single electron-transport 

 chains. The over-all rate of oxygen uptake as a result of tricarboxylic acid 

 cycle activity may likewise be limited by several steps (Montgomery and 

 Webb, 1956). When parallel pathways are simultaneously operating, as is 



