Bifunctional enzyme provides absolute concentration robustness in multisite covalent modification networks

DOI10.1007/S00285-024-02060-5arXiv2304.02679OpenAlexW4392391661MaRDI QIDQ6149820

Tung D. Nguyen, Badal Joshi

Publication date: 5 March 2024

Published in: Journal of Mathematical Biology (Search for Journal in Brave)

Abstract: Biochemical covalent modification networks exhibit a remarkable suite of steady state and dynamical properties such as multistationarity, oscillations, ultrasensitivity and absolute concentration robustness. This paper focuses on conditions required for a network to have a species with absolute concentration robustness. We find that the robustness in a substrate is endowed by its interaction with a bifunctional enzyme, which is an enzyme that has different roles when isolated versus when bound as a substrate-enzyme complex. When isolated, the bifunctional enzyme promotes production of more molecules of the robust species while when bound, the same enzyme facilitates degradation of the robust species. These dual actions produce robustness in the large class of covalent modification networks. For each network of this type, we find the network conditions for the presence of robustness, the species that has robustness, and its robustness value. The unified approach of simultaneously analyzing a large class of networks for a single property, i.e. absolute concentration robustness, reveals the underlying mechanism of the action of bifunctional enzyme while simultaneously providing a precise mathematical description of bifunctionality.

Full work available at URL: https://arxiv.org/abs/2304.02679

zbMATH Keywords

bifunctional enzymefutile cycleabsolute concentration robustnesscovalent modification networkparadoxical enzyme

Mathematics Subject Classification ID

Kinetics in biochemical problems (pharmacokinetics, enzyme kinetics, etc.) (92C45) Biochemistry, molecular biology (92C40) Systems biology, networks (92C42)

Cites Work

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