Importantly, Eqns ( )-( ) can only be applied to the onestep Mechanism A, in which case the apparent rate constant k obs depends on the inhibitor and enzyme concentrations as is shown in Eqn (6) (see Eqn. in the original paper ). Williams at al. have demonstrated that, specifically under tight-binding experimental conditions, it is theoretically impossible to derive any closed-form algebraic formula for the reaction progress under the two-step Mechanism B, similar to Eqn (4). According to these authors, the only possible way to obtain a mathematical model for the reaction progress under tight-binding conditions following Mechanism B is to perform a numerical integration of a relevant system of first-order ordinary differential equations (ODEs). Thus, it is fundamentally impossible to differentiate between the one-step Mechanism A and the two-steps Mechanism B on the basis of k obs data derived from the tightbinding rate Eqn (4), which only applies to the one-step binding mechanism.