EFFECTS OF TEMPERATURE: CELLULAR SYSTEMS 779 



hibition with temperature. It may be that some inhibitors would become 

 effective only at those temperatures at which the enzymes acted upon were 

 catalytically functional. 



Dependence of the Inhibition of Cell Function on Temperature 



It is generally true that the higher the level of functional activity of 

 a cell, the more readily is this function depressed by an enzyme inhibitor 

 (Chapter 9, page 464). Thus a muscle or a nerve will become more sensi- 

 tive to metabolic depression when it is stimulated more rapidly. It has 

 frequently been assumed that similar relations hold when the cell function 

 is altered by changes in the temperature. A cell or tissue whose functional 

 activity has been depressed by a reduction in the temperature would then 

 be expected to withstand inhibition better than at the normal temperature 

 because the metabolic energy requirement for the function is less. However, 

 the situation is somewhat different from that in which the function has 

 been modified independently of the metabolism. When a muscle is stimu- 

 lated at a lower frequency, the metabolism and levels of high-energy phos- 

 phate are not directly affected; if they change, it is a secondary result of 

 the altered functional activity. Whereas when the temperature is reduced, 

 the metabolic systems concerned with the formation and utilization of 

 high-energy phosphate are simultaneously reduced with the function. In 

 fact, the depression of functional activity by a fall in the temperature may 

 be due to the metabolic slowing. There is some evidence for this in the 

 similarity of the temperature characteristics for both respiration and func- 

 tion in a variety of cells, but this evidence is very tenuous. In any event, 

 when both function and the energy-supplying processes decrease simulta- 

 neously, the energy requirement relative to the rate of energy formation 

 need not become less. However, it may well take longer for an inhibition 

 to depress function because the availal^le high-energy phosphate will be 

 utilized more slowly. 



An interesting situation may arise when the rate at which a function 

 proceeds is directly correlated with the level of some high-energy compound, 

 such as ATP. Under normal conditions the concentration of ATP may 

 be near the optimal value and an increase will bring about no augmenta- 

 tion of the function. The presence of an inhibitor may reduce the ATP 

 concentration so that the functional activity occurs more slowly. If the 

 temperature is now increased, the level of ATP may rise and the function 

 may be at least partially restored. The degree of inhibition observed will 

 depend, therefore, on the two relationships — the cellular activity as a 

 function of the iVTP concentration and the ATP concentration as a func- 

 tion of the temperature — and the effects of an inhibitor on each. In 

 most cases, however, the functional processes will themselves be sensitive 

 to temperature changes. 



