title: A steady state mathematical model for stepwise "slow-binding" reversible enzyme inhibition.
abstract: The standard mathematical model for stepwise "slow-binding" enzyme inhibition (E+Iright harpoon over left harpoonEIright harpoon over left harpoonEI( *)) assumes that the initial enzyme-inhibitor complex EI is always at equilibrium with the free component species E and I. This assumption implies that the dissociation rate constant (EI-->E+I) is infinitely higher than the isomerization rate constant for EI-->EI( *). This paper presents a more general mathematical treatment, under the steady state approximation rather than the usual rapid-equilibrium approximation, whereby the two rate constants for the disappearance of EI are allowed to be comparable in magnitude. Experimentally relevant illustrative examples include discrimination between a single-step and a two-step mechanism for slow-binding inhibition kinetics.
authors.affiliation: BioKin Ltd, 15 Main Street, Suite 232, Watertown, MA 02472, USA. pksci01@biokin.com
authors.forename: Petr
authors.initials: P
authors.lastname: Kuzmic
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D016018:Least-Squares Analysis; D016014:Linear Models; D008956:Models, Chemical; D011485:Protein Binding; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors