General Chemical Reaction Network Theory for Olfactory Sensing Based on G-Protein-Coupled Receptors: Elucidation of Odorant Mixture Effects and Agonist-Synergist Threshold

This work presents a general chemical reaction network theory for olfactory sensing processes that employ G-protein-coupled receptors as olfactory receptors (ORs). The theory can be applied to general mixtures of odorants and an arbitrary number of ORs. Reactions of ORs with G-proteins, in both the presence and absence of odorants, are explicitly considered. A unique feature of the theory is the definition of an odor activity vector consisting of strengths of odorant-induced signals from ORs relative to those due to background G-protein activity in the absence of odorants. It is demonstrated that each component of the odor activity defined this way reduces to a Michaelis-Menten form capable of accounting for cooperation or competition effects between different odorants. The main features of the theory are illustrated for a two-odorant mixture. Known and potential mixture effects, such as suppression, shadowing, inhibition, and synergy, are quantitatively described. Effects of relative values of rate constants, basal activity, and G-protein concentration are also demonstrated.