title: Analysis of Ter-Ter enzyme kinetic mechanisms by computer simulation of isotope exchange at chemical equilibrium: development and application of ISOTER, a personal-computer-based program.
abstract: A convenient, personal-computer-based program has been developed that allows simulation of isotopic exchange kinetics at chemical equilibrium catalyzed by a three reactant-three product (TerTer) enzyme system: A + B + C integral of P + Q + R. This program, ISOTER, utilizes a rapid algebraic method to calculate the exchange rate between any reactant-product pair as a function of the substrate concentration and avoids altogether the necessity of deriving an explicit (but cumbersome and impractical) equation for exchange rate. ISOTER was used to generate model saturation patterns for 16 different TerTer kinetic mechanisms, varying different combinations of reactant-product pairs in constant ratio at equilibrium: [all substrates], [A, P], [B, Q], and [C, R], while holding the nonvaried components constant. These model studies indicate that virtually every one of these mechanisms can be distinguished from the others. In addition, ISOTER has been used to fit multiple sets of experimental data for Escherichia coli glutamine synthetase, which produced a set of rate constants consistent with the previously proposed "preferred order random" kinetic mechanism.
authors.affiliation: Department of Molecular & Cell Biology, P. M. Althouse Laboratory, Pennsylvania State University, University Park 16802.
authors.forename: F C
authors.initials: FC
authors.lastname: Wedler
authors.forename: R W
authors.initials: RW
authors.lastname: Barkley
mesh_terms: D003198:Computer Simulation; D004798:Enzymes / Q000378:metabolism*; D007700:Kinetics; D008433:Mathematics; D008838:Microcomputers; D008962:Models, Theoretical; D012984:Software
chemical_list: D004798:Enzymes