期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：16
页码：8884-8889
DOI：10.1073/pnas.1920873117
出版社：The National Academy of Sciences of the United States of America
摘要：One of the most intriguing features of biological systems is their ability to regulate the steady-state fluxes of the underlying biochemical reactions; however, the regulatory mechanisms and their physicochemical properties are not fully understood. Fundamentally, flux regulation can be explained with a chemical kinetic formalism describing the transitions between discrete states, with the reaction rates defined by an underlying free energy landscape. Which features of the energy landscape affect the flux distribution? Here we prove that the ratios of the steady-state fluxes of quasi–first-order biochemical processes are invariant to energy perturbations of the discrete states and are only affected by the energy barriers. In other words, the nonequilibrium flux distribution is under kinetic and not thermodynamic control. We illustrate the generality of this result for three biological processes. For the network describing protein folding along competing pathways, the probabilities of proceeding via these pathways are shown to be invariant to the stability of the intermediates or to the presence of additional misfolded states. For the network describing protein synthesis, the error rate and the energy expenditure per peptide bond is proven to be independent of the stability of the intermediate states. For molecular motors such as myosin-V, the ratio of forward to backward steps and the number of adenosine 5′-triphosphate (ATP) molecules hydrolyzed per step is demonstrated to be invariant to energy perturbations of the intermediate states. These findings place important constraints on the ability of mutations and drug perturbations to affect the steady-state flux distribution for a wide class of biological processes.
关键词：properties of biological processes ; nonequilibrium stationary dynamics ; kinetic control ; chemical kinetic analysis
