776 15. EFFECTS OF VAEIOUS FACTOES ON INHIBITION 



in making some adjustment to the presence of an inhibitor, are also sen- 

 sitive to temperature changes. Depression of terminal electron transport 

 by an inhibitor such as cyanide brings about a complex sequence of changes 

 in the levels of adenine nucleotides, which in turn accelerates the rates of 

 certain processes that tend to antagonize the respiratory depression. All 

 of these adjustments and their effectiveness will be altered by a variation 

 in the temperature. Both inhibitory and the related adaptive processes 

 change with temperature and the over-all result will not be readily inter- 

 pre table. 



Another factor that must be considered in certain experiments is the 

 effect of temperature on the concentrations of the enzymes and coenzymes 

 in the cells. The enzyme concentration will often depend on the balance 

 between the rates of formation and destruction, since there is a constant 

 turnover of most enzymes. The reactions may be written as: 



E^ ^ E ^ E, (15-47) 



where E^ is a precursor of the enzyme, E is the catalytically active enzyme, 

 and Ej is the inactive product of some process destroying the enzyme. The 

 level of (E) is important in determining the rate of the reaction this enzyme 

 catalyzes and may be altered by tem]3erature if the rates of the two reactions 

 are modified by temperature to different degrees. With regard to inhibition, 

 such changes in (E) would be esiiecially important in the study of very po- 

 tent inhibitors where the kinetics are those of zone B or zone C of mutual 

 depletion systems. The same principles would apply to coenzymes, such as 

 the diphosphopyridine and flavin adenine nucleotides. 



Certain metabolic processes appear to be organized on a structural basis, 

 the rapid rates and high efficiency arising from the compartmentalization 

 of the 'participating enzymes. Almost nothing is known of the effects of 

 temperature changes on such structures, except that the instability in- 

 creases at both low and high temperatures, and nothing at all is known of 

 how this may be related to the sensitivity to an inhibition. Work with iso- 

 lated mitochondria has shown that the metabolic characteristics are in- 

 timately correlated with the structural integrity, and it is very likely that 

 the response to an inhibitor will likewise be structure-dependent. 



Finally, one may look at the situation in a more general way. The meta- 

 bolic and functional operation of a cell occurs optimally only over a rather 

 narrow temperature range. Outside this range the cell becomes progressively 

 more deranged or damaged as the temperature is lowered or raised. It is 

 thus possible that in general a cell is most resistant to the detrimental ef- 

 fects of inhibitors in this optimal physiological range. It is here, perhaps, 

 that the cell is most nicely balanced and has the greatest buffer capacity 

 against metabolic disturbance. A cell that is already abnormal because of 



