Free-energy transduction mechanisms shape the flux space of metabolic networks - Laboratoire de Physique des Lasers, Atomes et Molécules
Article Dans Une Revue Biophysical Journal Année : 2024

Free-energy transduction mechanisms shape the flux space of metabolic networks

Résumé

The transduction of free energy in metabolic networks represents a thermodynamic mechanism by which the free energy derived from nutrients is converted to drive nonspontaneous, energy-requiring metabolic reactions. This transduction is typically observed in processes that generate energy-rich molecules such as ATP and NAD(P)H, which, in turn, power specific reactions, particularly biosynthetic reactions. This property establishes a pivotal connection between the intricate topology of metabolic networks and their ability to redirect energy for functional purposes. The present study proposes a dedicated framework aimed at exploring the relationship between free-energy dissipation, network topology, and metabolic objectives. The starting point is that, regardless of the network topology, nonequilibrium chemostatting conditions impose stringent thermodynamic constraints on the feasible flux steady states to satisfy energy and entropy balances. An analysis of randomly sampled reaction networks shows that the network topology imposes additional constraints that restrict the accessible flux solution space, depending on key structural features such as the reaction's molecularity, reaction cycles, and conservation laws. Notably, topologies featuring multimolecular reactions that implement free-energy transduction mechanisms tend to extend the accessible flux domains, facilitating the achievement of metabolic objectives such as anabolic flux maximization or flux rerouting capacity. This approach is applied to a coarse-grained model of carbohydrate metabolism, highlighting the structural requirements for optimal biomass yield.

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Chimie
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Dates et versions

hal-04772800 , version 1 (18-11-2024)

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Benjamin Pfeuty. Free-energy transduction mechanisms shape the flux space of metabolic networks. Biophysical Journal, 2024, 123 (20), pp.3600-3611. ⟨10.1016/j.bpj.2024.09.012⟩. ⟨hal-04772800⟩
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