Economic potentials in flux analysis
The metabolic fluxes in cells are governed by physical and economic principles. The stationarity condition constrains fluxes to a subspace in flux space, and thermodynamics requires fluxes to run from higher to lower chemical potentials, which constrains their sign patterns. At the same time, fluxes in cells represent a compromise between metabolic benefits and enzyme costs. To capture this compromise, some flux prediction methods optimise the fluxes for minimal costs, using heuristic cost terms. Economic flux analysis, in contrast, is based on the principle that fluxes should be realisable by kinetic models with optimal enzyme levels. The required balance between enzyme costs and metabolic benefits can be formulated using state variables called economic potentials, which capture the enzyme labour embodied in substances in the cell. Irrespective of specific kinetic details, fluxes must lead from lower to higher economic potentials. This resembles and complements the thermodynamic constraints and serves as a third type of constraint aside from stationarity and thermodynamics. Futile flux cycles, which would preclude a consistent choice of economic potentials, are defined algebraically and can be systematically detected and removed from flux distributions. Enzymes that participate in many possible cycles are likely targets of regulation. Economic flux analysis can predict high-yield and low-yield strategies and capture preemptive expression, multi-objective optimisation, and flux distributions spanning several symbiotic cells. Conceptually, it resembles the labour value theories in economics. It justifies and extends the principle of minimal fluxes and provides an intuitive framework to model the interplay of fluxes, metabolic control, and enzyme costs in cell metabolism.
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