Product dependence and bifunctionality compromise the ultrasensitivity of signal transduction cascades.

ABSTRACT: Covalent modification cycles are ubiquitous. Theoretical studies have suggested that they serve to increase sensitivity. However, this suggestion has not been corroborated experimentally in vivo. Here, we demonstrate that the assumptions of the theoretical studies, i.e., irreversibility and absence of product inhibition, were not trivial: when the conversion reactions are close to equilibrium or saturated by their product, "zero-order" ultrasensitivity disappears. For high sensitivities to arise, not only substrate saturation (zero-order) but also high equilibrium constants and low product saturation are required. Many covalent modification cycles are catalyzed by one bifunctional 'ambiguous' enzyme rather than by two independent proteins. This makes high substrate concentration and low pr

SUBMITTER: Ortega F 

PROVIDER: S-EPMC122162 | biostudies-literature | 2002 Feb

REPOSITORIES: biostudies-literature