Learning Regulation and Optimal Control of Enzyme Activities

Cannon, W. Roger; Britton, Samuel; Alber, Mark

doi:10.1016/j.bpj.2019.11.864

Cited by 1 publication

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This thermodynamic requirement coincides with recent experimental results that emphasize a near-equilibrium activity of PGI enzymes in various contexts [47], including oxidative bursts [48]. This latter result motivates us to refine our framework to integrate thermodynamic constraints as already implemented in some previous studies [5,7,9]. We consider the conservation relation s n + s nh = 1, defining a concentration unit.…”

Section: Discussionsupporting

confidence: 72%

“…Metabolic control analysis (MCA) provides a rigorous theoretical framework to study the sensitivity of metabolic networks with respect to biochemical and environmental variations [1,2]. MCA has been further developed and expanded in several directions related to regulation, thermodynamics, or statistical analysis [3][4][5][6][7][8][9]. These developments contribute to more comprehensive analysis of control properties of metabolic networks with the challenging goal to decipher the logic of complex regulation pattern, such as those involving direct metabolite-enzyme interactions and coupling distal parts of a network [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Control Analysis of Cooperativity and Complementarity in Metabolic Regulations: The Case of NADPH Homeostasis

2023

View full text Add to dashboard Cite

Complex feedback regulation patterns shape the cellular metabolic response to external or internal perturbations. We propose here a framework consisting of a sampling-based metabolic control analysis of kinetic models to investigate the modes of regulatory interplay in metabolic functions. NADPH homeostasis, for instance in a context of oxidative stress, is an example of metabolic function that involves multiple feedback regulations which raises the issue of their concerted action. Our computational framework allows us to characterize both respective and combined effects of regulations, distinguishing between synergistic versus complementary modes of regulatory crosstalk. Synergistic regulation of G6PD enzymes and PGI enzymes is mediated by congruent effects between concentration sensitivities and reaction elasticities. Complementary regulation of pentose phosphate pathway and lower glycolysis relates to metabolic state-dependent range of regulation efficiency. These cooperative effects are shown to significantly improve metabolic flux response to support NADPH homeostasis, providing a rationale for the complex feedback regulation pattern at work.

show abstract