448 



9. INHIBITION IN CELLS AND TISSUES 



tion if the enzyme inhibition is to be obtained, and Eq. 9-8 be rewritten 

 to show how this enzyme inhibition is related to the measured inhibition: 



i = it [1 + (VrlVs)] 



(9-9) 



Since v^ depends on the substrate concentration in many cases — and on 

 the particular substrate used also — the degree of inhibition will likewise 



Fig. 9-4. Graphical representation of inhi- 

 bitor-resistant metabolism. As the sensitive 

 fraction of the metabolism is inhibited, the 

 total metabolism will decrease as indicated 

 by this line. See Eq. 9-7. 



vary with the metabolic state of the cells and the availability of both en- 

 dogenous and exogenous substrates. The increased sensitivity to cyanide 

 of cells that are functionally activated (as during fertilization of marine 

 eggs, development of insect embryos, or germination of Neurospora spores) 

 may be related merely to the increased respiratory rate, due possibly to 

 greater availability of the substrate. 



The assumptions of this treatment should be borne in mind. The con- 

 stancy of the inhibitor-stable respiration, v^ under various conditions, 

 is probably approximate only. Examination of the graphs presented by 

 Commoner shows that deviation of the experimental points from the ideal 

 straight lines is marked in some cases. In determining accurately the in- 

 hibitor-stable fraction, it is necessary that the enzyme inhibited be com- 

 pletely blocked and since the top portion of the inhibition-concentration 

 curves is quite flat, total inhibition is sometimes not easy to obtain. For 

 example, in simple noncompetitive inhibition, if K^ = 0.1 mM, although 

 1 milf inhibitor will depress 91%, it requires 10 niM to inhibit 99%. Fur- 



