ArticleMolecular systems biology2026
Trade-off between flux efficiency and metabolic control shapes enzyme allocation.
Article in Molecular systems biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
Funding
Abstract
Efficient use of limited cellular resources is fundamental to metabolism. Although flux optimization is widely recognized as a central objective of metabolic networks, how flux efficiency influences the allocation of the metabolic proteome remains unclear and lacks direct validation. Here, we derive a simple analytical relationship linking the equilibrium constant (K) and the catalytic-abundance quotient (CAQ) of reactions within a pathway that defines the condition for maximal efficiency. By integrating reaction thermodynamics, enzyme kinetics, transcriptomic, and proteomic data, we compared enzyme allocation in glycolysis and the TCA cycle with this K-CAQ relationship across evolutionarily distant species, and showed that deviation from it can be explained by a trade-off between maximizing flux efficiency and concentrating flux control. Moreover, the drive to optimize glycolytic efficiency is strengthened under oncogenic signaling and a limited cellular budget for glycolytic enzymes. These findings establish a principle of Pareto optimality governing enzyme allocation in metabolic pathways and reveal key determinants of efficiency optimality in glycolysis.
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