The secant condition for instability in biochemical feedback control. I: The role of cooperativity and saturability (Q1175541)

This paper analyzes the oscillations arising in a sequence of biochemical reactions: \[ S_ 0 @>>>\underset{\downarrow} S_ 1 @>>>\underset{\downarrow} S_ 2 @>>> \dots @>>> S_ n @>>>\tag{1} \] in which the concentration of \(S_ 0\) is constant and the end-product, \(S_ n\), inhibits the formation rate of \(S_ 1\) from \(S_ 0\). A necessary condition for instability at the critical point is represented by the inequality: \[ (\beta_ 1\beta_ 2\dots \beta_{n- 1}\phi/\alpha_ 1\alpha_ 2\dots\alpha_ n)\geq (\text{sec }\pi/n)^ n,\tag{2} \] with \(\beta_ i\) the order of reaction of the formation of \(S_{i+1}\) from \(S_ i\); \(\alpha_ i\) the order of reaction of the combined processes of metabolic conversion and all other processes removing \(S_ i\); \(\phi\) the order of the negative feedback, and \(n\) the number of components. The order of a chemical reaction with respect to \(S_ i\) is defined as \(\partial\log V/\partial\log S_ i\), where \(V\) is the rate of reaction. The condition for instability is sufficient, if all the diagonal elements of the Jacobian matrix, \(a_ i\), are equal at the critical point and there is strict inequality. The proposed analysis makes a complete dissection, on a certain level, of the factors affecting local stability at the critical point, and shows how the inputs, model parameters, and qualitative features of the model will affect the reaction orders in equation (2) and the heterogeneity of the \(a_ i\). Section 3 studies the stability of a 3-component oscillatory model which has saturable final elimination and no feedback cooperativity. The effects of a saturable final elimination process and of a saturable elimination of an intermediate metabolite on the secant condition for instability are discussed in Sections 4 and 5.