Enzyme economy and metabolic control

TL;DR

This paper develops a theoretical framework linking enzyme levels, metabolic fluxes, and cellular benefit through economic principles, providing new insights into optimal metabolic states and enzyme economy.

Contribution

It introduces a novel metabolic value theory based on economic potentials and loads, unifying control theory with enzyme cost-benefit analysis.

Findings

Economic potentials and loads describe metabolite contributions to performance.

Optimal fluxes follow from local balance laws and economic principles.

Framework applies broadly to various rate laws and metabolic states.

Abstract

The metabolic state of a cell, comprising fluxes, metabolite concentrations and enzyme levels, is shaped by a compromise between metabolic benefit and enzyme cost. This hypothesis and its consequences can be studied by computational models and using a theory of metabolic value. In optimal metabolic states, any increase of an enzyme level must improve the metabolic performance to justify its own cost, so each active enzyme must contribute to the cell's benefit by producing valuable products. This principle of value production leads to variation rules that relate metabolic fluxes and reaction elasticities to enzyme costs. Metabolic value theory provides a language to describe this. It postulates a balance of local values, which I derive here from concepts of metabolic control theory. Economic state variables, called economic potentials and loads, describe how metabolites, reactions, and enzymes contribute to metabolic performance. Economic potentials describe the indirect value of metabolite production, while economic loads describe the indirect value of metabolite concentrations. These economic variables, and others, are linked by local balance equations. These laws for optimal metabolic states define conditions for metabolic fluxes that hold for a wide range of rate laws. To produce metabolic value, fluxes run from lower to higher economic potentials, must be free of futile cycles, and satisfy a principle of minimal weighted fluxes. Given an economical flux mode, one can systematically construct kinetic models in which all enzymes have positive effects on metabolic performance.