The membrane valve: A consequence of asymmetrical inhibition of membrane carriers. I. Equilibrating transport systems

Facilitated membrane transport systems act as valves, or rectifiers, when the substrate affinities on the two sides of the membrane differ substantially, i.e. when the system is strongly asymmetric. The asymmetry may be intrinsic or imposed by a reversible competitive inhibitor acting on only one side of the membrane. Under non-equilibrium conditions such systems allow net movements of substrate to proceed faster, sometimes much faster, in one direction than the other, though the final equilibrium is unaffected. Obligatory exchange systems may also function as valves when inhibited unsymmetrically, permitting exchange to occur more rapidly with one distribution of substrates than with the reversed distribution. Here, unequal flux rates do not depend on unequal concentrations of the substrate on either side of the membrane, but may also occur with equal concentrations, provided the affinities of the two substrates differ.The kinetic theory leading to these conclusions is given here, and it is shown how individual parameters of a carrier system affect the efficiency, or tightness, of the valve. In addition, simple kinetic tests for the operation of a valve are outlined. Examples are cited of transport systems having inhibitor-binding sites on only one surface of the cell membrane, which could function normally as valves. Systems implicated are glucose transport in various cells, the ADP-ATP exchanger of mitochondria, the anion transporter of erythrocytes, and the Na⁺-K⁺ pump.