Phosphorylation Energy Hypothesis: Open Chemical Systems and Their Biological Functions

Biochemical systems and processes in living cells generally operate far from equilibrium. This review presents an overview of a statistical thermodynamic treatment for such systems, with examples from several key components in cellular signal transduction. Open-system nonequilibrium steady-state (NESS) models are introduced. The models account quantitatively for the energetics and thermodynamics in phosphorylation-dephosphorylation switches, GTPase timers, and specificity amplification through kinetic proofreading. The chemical energy derived from ATP and GTP hydrolysis establishes the NESS of a cell and makes the cell—a mesoscopic–biochemical reaction system that consists of a collection of thermally driven fluctuating macromolecules—a genetically programmed chemical machine.