A hypothesis for the role of dithiol-disulfide interchange in solute transport and energy-transducing processes.
We have recently shown that the physical mechanism for delta approximately mu H+-driven changes in the Km 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. Natl Acad. Sci. USA, 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 membrane-related 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, delta psi, or a pH gradient, delta pH, can alter the redox state, it can change the affinity of the substrate-binding sites. The delta approximately mu H+-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 delta approximately mu 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 delta approximately mu H+. The ligand-binding affinities of facilitated diffusion transport systems and receptor proteins may be regulated in this manner.
D001665:Binding Sites; D001692:Biological Transport; D004220:Disulfides / Q000378:metabolism*; D004563:Electrochemistry; D004735:Energy Transfer; D008433:Mathematics; D008564:Membrane Potentials; D008956:Models, Chemical; D010084:Oxidation-Reduction; D011522:Protons; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D004220:Disulfides; D011522:Protons; D013438:Sulfhydryl Compounds