The interaction between full and partial inhibitors acting on a single enzyme. A theoretical analysis

P Palatini

A theoretical analysis has been made of multiple inhibition systems involving a full and a partial inhibitor. This analysis applies to single- and multisubstrate enzyme systems obeying Michaelis-Menten kinetics. It has been shown that a plot of the reciprocal of the enzyme velocity versus the concentration of the full inhibitor, at constant substrate concentration, is linear in either the presence or the absence of a fixed level of the partial inhibitor. If the slope of the plot is increased or unaltered in the presence of a fixed concentration of the partial inhibitor, the two inhibitors are mutually nonexclusive. If the slope of the plot is decreased, the two inhibitors may be either mutually exclusive or nonexclusive. When a decrease in slope is observed, mutual exclusivity can be distinguished from nonexclusivity by the use of secondary plots based on the effect of the partial inhibitor on the slope or the abscissal intercept of the primary plot. The rules proposed for distinguishing mutually exclusive from nonexclusive inhibitors hold irrespective of the type of inhibition (competitive, noncompetitive, uncompetitive, mixed), so that a knowledge of the kinetic nature of the inhibitors is not required. The results of such an analysis are also discussed in terms of summation, antagonism, and synergism between inhibitors. It has been pointed out that independent inhibitor binding does not necessarily result in independent inhibitor effects, and the conditions necessary for observation of independent inhibitory effects have been defined.

Volume 24, Issue 1, pp. 30-41, 07/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics