title: A model study of sequential enzyme reactions and electrostatic channeling.
abstract: We study models of two sequential enzyme-catalyzed reactions as a basic functional building block for coupled biochemical networks. We investigate the influence of enzyme distributions and long-range molecular interactions on reaction kinetics, which have been exploited in biological systems to maximize metabolic efficiency and signaling effects. Specifically, we examine how the maximal rate of product generation in a series of sequential reactions is dependent on the enzyme distribution and the electrostatic composition of its participant enzymes and substrates. We find that close proximity between enzymes does not guarantee optimal reaction rates, as the benefit of decreasing enzyme separation is countered by the volume excluded by adjacent enzymes. We further quantify the extent to which the electrostatic potential increases the efficiency of transferring substrate between enzymes, which supports the existence of electrostatic channeling in nature. Here, a major finding is that the role of attractive electrostatic interactions in confining intermediate substrates in the vicinity of the enzymes can contribute more to net reactive throughput than the directional properties of the electrostatic fields. These findings shed light on the interplay of long-range interactions and enzyme distributions in coupled enzyme-catalyzed reactions, and their influence on signaling in biological systems.
authors.affiliation: Howard Hughes Medical Institute, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Changsun
authors.initials: C
authors.lastname: Eun
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Kekenes-Huskey
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Metzger
authors.affiliation: Howard Hughes Medical Institute, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon
mesh_terms: D004798:Enzymes / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D055672:Static Electricity
chemical_list: D004798:Enzymes