GENERALIZED KINETICS OF REVERSIBLE INHIBITION 



61 



tations. The usual terminology will be followed in this book because it is 

 so deeply implanted in the literature on enzyme inhibition and it is hoped 

 that the terms will be understood in the most general way, so that they will 

 not imply particular mechanisms on the molecular level. 



Inhibition of Enzyme Systems for Which Steady-State Kinetics Are Necessary 



The equations presented above (3-12 to 3-15) for competitive inhibition 

 are valid for steady-state systems and K^ may be replaced by K,,^. However, 

 for the non-competitive inhibition of steady-state systems, where K^,^ = 

 (A;_i+A'2)/Z.'i or depends on more complex combinations of the rate constants, 

 the presence of the inhibitor will alter iii,,, as well as F,„. since the rate of 

 breakdow^n of the critical complex will be a factor in both K,,^ and F,„, 

 and this rate will be modified by the inhibitor as pointed out by Dixon and 

 Webb (1958, p. 179). Pure noncompetitive inhibition would thus be im- 

 possible in steady-state systems where K,,^ does not represent the substrate 

 constant. Noncompetitive inhibitors acting on such systems will therefore 

 be classed as mixed from the forms of the reciprocal plots. This was stated 

 in a somewhat different manner by Morales (1955). when he concluded that 

 if inhibition kinetics are noncompetitive, the Michaelis constant is an equi- 

 librium constant. 



Dependence of Inhibition on Substrate and Inhibitor Concentrations 



The variations in rate and inhibition with substrate and inhibitor concen- 

 tration are plotted in Figs. 3-2 to 3-5 for the common types of inhibition. 



PS- 



Fig. 3-2. Variation of the rate with substrate concentration for different types of 

 inhibition. pS is — log (S) when (S) is M. A%= 1 milf. A', = 0.1 mif, A'/ = 0.1 ml/, 

 (I) = 0.3 m3/, and F„j = 100. Curve I: uninhibited; curve II: competitive inhi- 

 bition; cui've III: noncompetitive inhibition; curve IV: coupling inhibition. 



