778 15. EFFECTS OF VARIOUS FACTORS ON INHIBITION 



usudl is respiration, it is extremely difficult to attribute the over-all rate 

 to any one i)rocess. The change in the rate with tem])erature can thus not 

 be interpreted directly. 



The presence of an inhibitor will modify the respiratory pattern in a 

 complex fashion, even though the inhibition is specific on a single type of 

 enzyme. The effects of temperature changes on this inhibition may be 

 attributed to a variety of factors, some of which have been discussed above. 

 In many cases, the effect will have little or nothing to do with the primary 

 inhibition. For example, if the inhibitor acts on one of several parallel 

 pathways, a change in the temperature may either increase or decrease the 

 over-all inhibition depending on the relative sensitivities of these pathways 

 to temperature. When a noninhibited pathway has a relatively high tem- 

 perature coefficient, a rise in temperature will lead to a greater contribution 

 by this pathway and the inhibition may l)e reduced, this effect having noth- 

 ing to do with the possible changes in the inhibition itself, and, in fact, 

 being superimposed upon it. Such interpretations as have been made of the 

 rise in the inhibition of RhizohitDn respiration by urethane as the temper- 

 ature is increased, this being attributed to a facilitation of enzyme inac- 

 tivation, must be critically examined (Koffier et al., 1947). Many other fac- 

 tors should be eliminated before the results can be related to only a single 

 process. • Respiration has been used here as an example of any complex 

 metabolic activity of the cell and the same principles would apply to all. 



Naturally Occurring Heat-Labile Enzyme Inhibitors 



It has been found that certain intracellular enzymes become much more 

 active as the temperature is raised, this occurring rather suddenly over a 

 small temperature range and with a temperature coefficient higher than 

 would be expected for any enzyme reaction. Indeed, these enzymes appear 

 to be completely inactive at the normal temperature. The mechanism of 

 this "heat activation" of enzymes was elucidated by Swartz et al. (1957) 

 for the DPN-pyrophosphatases of certain bacteria ( Proteus species, My- 

 cohacteriiuH hutyricum, Bacillus subtilis, and Staphylococcus aureus). These 

 enzymes when extracted from the cells are inactive and become active 

 when the temperature rises above 40^. This is due to the destruction of 

 a natural inhibitor at these higher temperatures. These inhibitors are prob- 

 ably protein and within the normal cells are bound to the enzymes quite 

 tightly. 



It is not known how widespi'ead this phenomenon may be, nor if it occurs 

 in cells other than bacteria. Certainly many naturally occurring inhibitors 

 for a wide variety of enzymes have been demonstrated and it is quite possi- 

 ble that these inhibitors, or at least the combination with the enzymes, 

 may be sensitive to temperature changes. Such behavior would be of im- 

 portance in the response of cells to inhibitors and the variation of this in- 



