Coupling of vectorial proton flow to a biochemical reaction by local electric interactions.

Abstract

For a transmembrane redox enzyme and a (passive) protonophore, the complete set of rate equations is given. Turnover causes cyclic variation of their electric polarization. This is responsible not only for effects of the electric field on the rate constants but also for the generation of an electric field felt by neighboring molecules. It is calculated that, when the systems are close together at a fixed distance, cycling of the two systems becomes coupled enabling the protonophore to pump protons against their electrochemical gradient. If the electrochemical gradient for protons approaches the input force of the redox reaction, slip (incomplete coupling between the chemical and proton-transport reactions) results. By using different sets of parameters, both kinetically reversible and kinetically irreversible proton pumps can be simulated.Although the involvement of protons in several bioenergetic processes (see ref. 1) is widely acknowledged, the molecular mechanism as well as the stoichiometry (2-4) of proton pumping by membrane-bound proteins remains uncertain. Two lines of thought concerning the mechanism of coupling between vectorial proton flow and biochemical reactions may be distinguished. The first hypothesizes that covalent integration of the pathways of the chemical and pumping reactions is catalyzed by the membrane-bound enzyme (5). The second hypothesizes that the biochemical reaction and vectorial pumping activities take place at different sites on the membrane-embedded enzyme, the free-energy transfer being mediated by the enzyme (6-10).More obviously than the former, the latter mechanism allows for "slip"-i.e., incomplete coupling between the chemical and proton-transport reactions (2)-and, therefore, for proton stoichiometries depending on the balance between the applied thermodynamic forces (for review, see ref. 1). Slip has been experimentally demonstrated in various cases, including the proton pumps involved in oxidative phosphorylation (2-4), the Ca2+-ATPase (11), bacteriorhodopsin (12), and DNA gyrase (13). Fig. 1A shows a kinetic diagram of a proton pump that may display slip. One site (on the translocator part of the pump) may bind or release a proton at either side of the membrane and can go, either without or with a bound proton, from one side of the membrane to the other. Another site (on the enzyme part) can bind a substrate (e.g., NADH, cytochrome c, or ATP), convert it, and release product. Coupling is ensured if the slip transition (Fig. LA) is improbable (1, 14). Although schemes of this sort have been widely applied to studies of slip-related phenomena (e.g., refs. 1, 14-16), they do not explain explicitly what the molecular basis for the restriction on the slip transition 1s.In this paper we present a different type of model for a proton pump. We considered two parts (e.g., subunits) of an enzyme complex, one capable of transporting protons across a membrane (the translocator), the other catalyzing a biochemical reaction (the enzyme) (see Fig. 1B). We will show that if t...

How Yeast Cells Synchronize their Glycolytic Oscillations: A Perturbation Analytic Treatment

“…This bilateral entrainment (cf. Perez et al (1996), Martinez De La Fuente et al (1995, and Kamp et al (1988) for a case with implications for free-energy transduction) is an example of self-organizing dynamics of a biological system (Glansdorff and Prigogine, 1971;Hess and Mikhailov, 1994). Understanding of cell-cell interaction may more generally be important in the analysis of cases where a population of actual cells behaves nonchaotically, whereas the dynamics of an individual cell allow chaos (Movileanu and Flonta, 1992).…”

A Role for Tim21 in Membrane-Potential-Dependent Preprotein Sorting in Mitochondria

“…In contrast, the motor-bound form of the presequence translocase does not interact with III-IV supercomplexes to a significant degree, and therefore, preprotein translocation into the matrix is more sensitive to a reduction of Dc; here, the ATP-dependent motor drives the completion of transport. Biophysical studies have implicated that the proton-motive force is not of identical magnitude over an entire energy-coupling membrane but that local differences can exist, and this leads to zones of increased membrane potential in the direct vicinity of proton-pumping complexes [22][23][24][25]. The direct coupling of TIM23 SORT to the respiratory chain thus explains the apparently paradoxical observation that the Dcdependence of preproteins with identical net charge is strikingly different depending on the presence of an inner-membrane-sorting signal [16].…”

Stochastically pumped adaptation and directional motion of molecular machines

“…Every time the ion channel opens or closes, the local electric field across the membrane changes, and because the flow of ions down the electrochemical gradient when the channel is open dissipates energy, the resulting electrical noise is a nonequilibrium fluctuation. These fluctuations, when coupled to conformational transitions of the transporter, can provide energy to drive transport of S from low to high chemical potential, even if S itself is uncharged (1,2). The mechanism by which this occurs is known as electroconformational coupling (3)(4)(5).…”