A Hypothesis for the Role of Dithiol‐Disulfide Interchange in Solute Transport and Energy‐Transducing Processes

Abstract

We have recently shown that the physical mechanism for A,GH+-driven changes in the K, for three different transport systems is an oxidation-reduction reaction involving a dithiol-disulfide interconversion [Robillard, G. T. and Konings, W. N. (1981) Biochemistry, 20, 5025-5032;Konings, W. N. and Robillard, G. T. (1982) Proc. Nut1 Acad. Sci. U S A , in the press]. Based on the similarities between the data from these three systems and published data from other systems, we now propose that dithiol-disulfide interchange may play a general role in membranerelated processes such as transport, energy transduction and hormone-receptor interactions.We propose that the affinities of the substrate-binding sites are regulated by a dithiol and a disulfide situated at different depths in the membrane. In addition we propose that the oxidation states of these two redox centers are coupled by dithiol-disulfide interchange such that. when one is oxidized, the other is reduced. Since a transmembrane electrical potential, A $ , or a pH gradient, ApH, can alter the redox state, it can change the affinity of the substratebinding sites. The Afii,+-induced changes in affinity are sufficient to drive active transport (symport or antiport) and energy-transducing processes. A similar mechanism can be applied to transport systems driven by phosphorylated enzyme intermediates instead of A f i H + .Changes of the redox potential in a given compartment during metabolism could also control the affinity of ligand binding even in the absence of a A , i i~+ .The ligand-binding affinities of facilitated diffusion transport systems and receptor proteins may be regulated in this manner.