586 



12. RATES OF INHIBITION 



if any correlation exists between the metabolic pathways disturbed and 

 the activity of the cell. Holmes (1933) perfused frogs with media containing 

 iodoacetate at different concentrations and found that the glycolysis was 

 inhibited fairly rapidly (Fig. 12-29) in the brain, followed by a fall in the 

 creatine phosphate levels. However, nerve function, as evidenced by the 

 ability to respond to strychnine, did not fall appreciably during this phase 

 and began to be depressed only after glycolysis was 90% blocked, after 

 which it decreased linearly to a complete loss of function. Nevertheless, it 

 is not justifiable to conclude that function is unrelated to glycolysis or 



20 40 60 

 TIME (MINUTES) ► 



Fig. 12-28 Inhibition of glycolysis in Streptobacterium 

 casei by iodoacetate (1.1 milf). This curve does not 

 include the long latent period before inhibition begins. 

 The bimolecular rate constant. ^^ would be 6.9 X lO-"* 

 or the bimolecular rate constant (with one reactant in 

 excess) would be 40 liters mole~^ niin~^ (From Field 

 and Field, 1932 b.) 



creatine phosphate. In the first place, one does not know just how far it 

 is i3ossible to lower glycolysis or creatine phosj^hate without disturbing the 

 function; a fair margin of safety might occur in normal tissue. In the second 

 place, it is now known that it is probably not the creatine phosphate level 

 which is functionally important, but the level of ATP, which can remain at 

 near normal values until the creatine phosphate has fallen below a critical 

 concentration. In any event, such behavior illustrates well the varying 

 rates at which different processes in the cell can be altered by an inhibitor. 

 Iodoacetate depresses cardiac function slowly and an attempt was made 

 by Gardner et al. (1954) to elucidate some of the controlling factors. They 

 determined how the rate of inhibition was altered by changes in iodoace- 

 tate concentration, temperature, and beat freciuency (Fig. 12-30). At 37° 

 the contractility of rabbit atria is more sensitive to iodoacetate than is 

 the spontaneous rate (curves A and B) and a difference is also seen in the 



