Titre :

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

Auteur(s) :

Pfeuty, Benjamin [Auteur]
Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 [PhLAM]
Hurbain, Julien [Auteur]
Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 [PhLAM]
Thommen, Quentin [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]

Titre de la revue :

Metabolites

Pagination :

485

Éditeur :

MDPI

Date de publication :

2023-04

ISSN :

2218-1989

Mot(s)-clé(s) en anglais :

regulation metabolism control analysis kinetic model
regulation
metabolism
control analysis
kinetic model

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

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 ...
Lire la suite >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.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL