Metabolic Structure: A Paradigm Revisited in Light of the Fundamental Parameters of Living Systems

Abstract

ABSTRACT The concept of ‘metabolic structure’, which considers metabolism as a stable, genetically encoded architecture with enzymes occupying fixed control positions, is indispensable but incomplete, and it obscures metabolism's true nature. I propose redefining metabolism as a dynamic field of emergent biochemical fluxes, governed by six fundamental parameters: time, water, entropy, quantum effects, space, and electrostatic potential, shaping the thermodynamic trajectories of living matter. Metabolic control analysis already supports this view: flux control coefficients are state‐ and time‐dependent coordinates within a thermodynamic field, not intrinsic enzyme properties. This perspective manifests across scales: electrostatics govern fructose 1,6‐bisphosphate cleavage in aldolase; hepatic zonation shows spatial reorganization through a single parameter; glucose deprivation quantitatively redirects intestinal cancer cell metabolism from glycolytic to oxidative flux, driving differentiation into an enterocyte‐like state; post‐meal walking redirects glucose flux from storage to oxidation without pharmacological intervention; inherited metabolic diseases can sometimes be managed without correcting the causal mutation. These examples converge into a new framework: metabolism possesses not only a sophisticated architecture but also states that shape its fluxes. And states, unlike static structures, can be reconfigured.