How enzyme economy shapes metabolic fluxes

Metabolic fluxes are governed by physical and economic principles. Stationarity constrains them to a subspace in flux space and thermodynamics makes them lead from higher to lower chemical potentials. At the same time, fluxes in cells represent a compromise between metabolic performance and enzyme cost. To capture this, some flux prediction methods penalise larger fluxes by heuristic cost terms. Economic flux analysis, in contrast, postulates a balance between enzyme costs and metabolic benefits as a necessary condition for fluxes to be realised by kinetic models with optimal enzyme levels. The constraints are formulated using economic potentials, state variables that capture the enzyme labour embodied in metabolites. Generally, fluxes must lead from lower to higher economic potentials. This principle, which resembles thermodynamic constraints, can complement stationarity and thermodynamic constraints in flux analysis. Futile modes, which would be incompatible with economic potentials, are defined algebraically and can be systematically removed from flux distributions. Enzymes that participate in potential futile modes are likely targets of regulation. Economic flux analysis can predict high-yield and low-yield strategies and captures preemptive expression, multi-objective optimisation, and flux distributions across several cells living in symbiosis. Inspired by labour value theories in economics, it justifies and extends the principle of minimal fluxes and provides an intuitive framework to model the complex interplay of fluxes, metabolic control, and enzyme costs in cells.