Activated phosphorylation-dephosphorylation biochemical reaction cycles are a class of enzymatic futile cycles.A futile cycle such as a single MAPK cascade governed by two underlying enzymatic reactions permits Hyperbolic (H), Signal transducing (ST), Threshold-hyperbolic (TH) and Ultrasensitive (U) operating regimes that characterize input-output behaviour.Retroactive signalling caused by load due to sequestration of phosphorylated or unphosphorylated form of the substrate in a single enzymatic cascade without hellfire sloe gin explicit feedback can introduce two-way communication, a feature not possible otherwise.We systematically characterize the operating regimes of a futile cycle subject to retroactivity in either of the substrate forms.We demonstrate that increasing retroactivity strength, which quantifies the downstream load, can trigger five possible regime transitions.
Retroactivity strength is a reflection of the fraction of the substrate sequestered by its downstream target.Remarkably, the minimum required retroactivity strength to evidence any sequestration triggered regime transition demands 23% of the substrate bound to its downstream target.This read more minimum retroactivity strength corresponds to the transition of the dose-response curve from ST to H regime.We show that modulation of the saturation and unsaturation levels of the enzymatic reactions by retroactivity is the fundamental mechanism governing operating regime transition.