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

TL;DR

This paper develops a comprehensive chemical reaction network theory for olfactory sensing that models odorant mixture effects and receptor interactions, providing quantitative insights into phenomena like suppression, synergy, and inhibition.

Contribution

It introduces a general theoretical framework for olfactory receptor responses to odorant mixtures, accounting for cooperation and competition effects with explicit reaction dynamics.

Findings

The theory describes various mixture effects such as suppression, shadowing, and synergy.

It demonstrates how odorant-receptor interactions can be modeled with Michaelis-Menten kinetics.

Effects of rate constants, basal activity, and G-protein levels on receptor responses are quantified.

Abstract

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 is applicable to general mixtures of odorants and an arbitrary number of ORs. Reactions of ORs with G-proteins, both in the presence and the 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.