Testing carrier models of cotransport using the binding kinetics of non-transported competitive inhibitors.

The kinetic equations representing the binding of a non-transported competitive inhibitor are derived from three variations of the carrier model of cotransport. These are (a) the model in which the binding sequence of activator and substrate is random (random bi-bi); (b) the model in which activator must bind before substrate (ordered bi-bi, activator essential), and (c) the model in which substrate must bind before activator (ordered bi-bi, activator non-essential). In general it is found that the kinetic equations for inhibitor binding are considerably simpler and easier to test than the corresponding transport equations. The effect of trans-inhibitor, transported substrate, activator concentration and membrane potential on inhibitor binding are examined in some detail. The use of these results to test and characterize the three transport models is emphasized. Applications to transport mechanisms which are not of the mobile carrier type are also discussed. A summary of relevant experimental data interpreted in terms of the theoretical models concludes the paper.