Potential misconceptions arising from the application of enzyme kinetic equations to ligand-receptor systems at equilibrium.

The interactions of ligands with their receptors and the modulation of those interactions by other ligands are commonly described in the (verbal and mathematical) language of enzymology. While this analogy is appropriate in that velocity-substrate concentration curves and ligand-receptor binding isotherms often conform to similar rectangular hyperbolic relationships, the mathematical and conceptual similarities between the two systems strictly apply only to the simplest cases (absence or presence of a pure competitive inhibitor). To conclude that other classic forms of enzyme inhibition (uncompetitive, noncompetitive, mixed) have their exact mechanistic counterparts in "receptorology" can be misleading if due consideration is not given to the differences between the two types of system (steady-state versus equilibrium). In this communication, it is shown that relating receptor binding mechanisms to enzymological models results in Scatchard plots that are markedly different in appearance from the equivalent Eadie plots displaying enzyme kinetic data for all cases other than those in the absence of inhibitor or in the presence of a purely competitive inhibitor. It follows that receptor binding systems, which do produce inhibition patterns similar to those indicative of uncompetitive, noncompetitive, or mixed inhibition of an enzyme system, must do so through mechanisms that are different from those that produce these effects on enzymes. Consequently, terms such as uncompetitive or noncompetitive inhibition have different meanings when applied to receptors as compared with enzymes.