Trade-off between flux efficiency and metabolic control shapes enzyme allocation
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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BibTeX
@article{sun2026tradeoff,
title = {{Trade-off between flux efficiency and metabolic control shapes enzyme allocation}},
author = {Kai Sun and Weiyan Zheng and Wenchao Fan and Chuyun Ding and Dan Huang and Ziwei Dai},
journal = {Molecular Systems Biology},
year = {2026},
month = oct,
doi = {10.1038/s44320-026-00250-5},
url = {https://link.springer.com/10.1038/s44320-026-00250-5},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Trade-off between flux efficiency and metabolic control shapes enzyme allocation
AU - Kai Sun
AU - Weiyan Zheng
AU - Wenchao Fan
AU - Chuyun Ding
AU - Dan Huang
AU - Ziwei Dai
PY - 2026
DA - 2026/10/04
JO - Molecular Systems Biology
DO - 10.1038/s44320-026-00250-5
UR - https://link.springer.com/10.1038/s44320-026-00250-5
AB - 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.
SN - 1744-4292
ER -