Stochastic theory of nonequilibrium steady states. Part II: Applications in chemical biophysics

The mathematical theory of nonequilibrium steady state (NESS) has a natural application in open biochemical systems which have sustained source(s) and sink(s) in terms of a difference in their chemical potentials. After a brief introduction in Section 1, in Part II of this review, we present the widely studied biochemical enzyme kinetics, the workhorse of biochemical dynamic modeling, in terms of the theory of NESS (Section 2.1). We then show that several phenomena in enzyme kinetics, including a newly discovered activation–inhibition switching (Section 2.2) and the well-known non-Michaelis–Menten-cooperativity (Section 2.3) and kinetic proofreading (Section 2.4), are all consequences of the NESS of driven biochemical systems with associated cycle fluxes. Section 3 is focused on nonlinear and nonequilibrium systems of biochemical reactions. We use the phosphorylation–dephosphorylation cycle (PdPC), one of the most important biochemical signaling networks, as an example (Section 3.1). It starts with a brief introduction of the Delbrück–Gillespie process approach to mesoscopic biochemical kinetics (Sections 3.2 and 3.3). We shall discuss the zeroth-order ultrasensitivity of PdPC in terms of a new concept — the temporal cooperativity (Sections 3.4 and 3.5), as well as PdPC with feedback which leads to biochemical nonlinear bistability (Section 3.6). Also, both are nonequilibrium phenomena. PdPC with a nonlinear feedback is kinetically isomorphic to a self-regulating gene expression network, hence the theory of NESS discussed here could have wide applications to many other biochemical systems.