Analysis and modification of nonhyperbolic kinetic models

Abstract

A nonhyperbolic model of Rabin (Biochem J 1967, 102, 22C-23C) in which four conformational states are considered has been simplified to the three-state one. Only multistate models (if the concentration of enzyme or receptor is assumed to be low) can yield nonhyperbolic kinetics. The simplified model has been shown to retain all the essential properties of the original four-state model. The model yields a diversity of nonhyperbolic dose-response curves both with higher and lower steepness than that of Henri-type ones. The three-state model can be further reduced to the hyperbolic one by making identical the different (unliganded) states. The bistate model in which protein concentration is assumed to be high yields nonhyperbolic kinetics as well; the model is reduced to the hyperbolic one if the protein concentration is assumed to be low.