Testing the simple carrier using irreversible inhibitors

Abstract

1. We analyse the kinetics of irreversible inhibition of the simple carrier. We consider how the rate of inactivation is influenced by the concentrations of permeant on the two sides of the membrane. 2. We consider various kinetic schemes for the simple carrier and show that these are all indistinguishable kinetically, using steady-state transport or inactivation data. We point out the advantages of using the simplest kinetic scheme and the possible pitfalls of using more complicated schemes, including the conventional carrier model. 3. We show that in the absence of information on the transport properties of the system, irreversible inhibition data are ambiguous. Taken together with transport data, however, inactivation data provide new tests for the applicability of the simple carrier. 4. The new tests show that for the simple carrier model to be applicable, the substrate dependencies of transport and of inactivation must be identical in comparable experimental situations. Further, the maximal rates of transport and of stimulation (or inhibition) of inactivation must obey a simple relationship, which we derive. We illustrate the use of these tests with published data on the glucose and choline transport systems of the human red blood cell.