Thermodynamics of Metabolic Pathways

Metabolic engineering involves designing manipulations of the native biochemistry to force the production of biochemical compounds. During the design process, it is important to account for the thermodynamic feasibility of the metabolic reactions involved in the pathways that produce these biochemical compounds as well as the physiological conditions within cells. The thermodynamic feasibility of a reaction is governed by its Gibbs free energy. This free energy can be calculated from the standard Gibbs free energy of formation of the reactants, their concentrations, and the physiochemical conditions of the cell. Thermodynamics was introduced to describe the relation of heat, work, and temperature with energy and matter. The two most fundamental laws of thermodynamics are the first law of thermodynamics, which states that all energy is conserved, and the second law of thermodynamics which states that the entropy production of any process is larger than or equal to zero. In the field of biochemistry, these physical principles are applied to analyze the chemical processes underlying energy transductions in living matter. In particular, the Gibbs free energy determines the direction in which a chemical reaction occurs spontaneously. Based on the second law of thermodynamics, and the relation of the Gibbs free energy to the entropy, a chemical reaction will be spontaneous in the direction that results in a negative Gibbs free energy. The Gibbs free energy can be calculated from the standard Gibbs free energy of formation of the reactants, their concentration, and the physical properties of their environment. Applying these physical principles to the biochemical reactions that constitute metabolism creates a direct link between the concentrations of the metabolites and the reaction directionalities. This knowledge, combined with mathematical modeling, helps to identify the cellular phenotypes and to engineer organisms to produce biochemicals.