Coupled proton pump

Rich (1995) has proposed that the proton pump in cytochrome c oxidase is driven mainly by electrostatic interactions (or repulsion) between protons in a proton trap and protons transferred from the matrix side to the O2 reduction site for neutralizing oxides (O ) are produced by O2 reduction. In this mechanism, a structural change for gating proton transfer from the matrix side to the proton trap is required for a complete cycle of redox-coupled proton pumping. However, no such structural change has been detected. 

An indirectly coupled proton pump principle was originally suggested in connection with the b cycle [14]. However, the directly coupled alternative of Fig. 3.12B is... 

FIGURE 2.3 The three main families of mammalian G-protein-coupled 7TM receptors in mammals. No obvious sequence identity is found between the rhodopsin-like family A, the glucagon/VIP/calcitonin family B, and the metabotropic glutamate/chemosensor family C of G-protein-coupled 7TM receptors, with the exception of the disulfide bridge between the top of TM-III and the middle of extracellular loop-2 (see Figure 2.2). Similarly, no apparent sequence identity exists among members of these three families and, for example the 7TM bitter taste receptors, the V1R pheromone receptors, and the 7TM frizzled proteins, which all are either known or believed to be G-protein-coupled receptors. Bacteriorhodopsins, which are not G-protein-coupled proteins but proton pumps, are totally different in respect to amino-acid sequence but have a seven-helical bundle arranged rather similarly to that for the G-protein-coupled receptors. 

Belevich I, Verkhovsky MI, Wikstrom M (2006) Proton-coupled electron transfer drives the proton pump of cytochrome c oxidase. Nature 440 829-832. 

The oxidation/reduction of redox cofactors in biological systems is often coupled to proton binding/release either at the cofactor itself or at local amino acid residues, which provides the basic mechanochem-ical part of a proton pump such as that foimd in cytochrome c oxidase (95). Despite a thermodynamic cycle that provides that coupling of protonation of amino acids to the reduction process will result in a 60 mV/pH decrease unit in the reduction potential per proton boimd between the pAa values in the Fe(III) and Fe(II) states, the essential pumping of protons in the respiratory complexes has yet to be localized within their three-dimensional structures. 

Proton gradients can be built up in various ways. A very unusual type is represented by bacteriorhodopsin (1), a light-driven proton pump that various bacteria use to produce energy. As with rhodopsin in the eye, the light-sensitive component used here is covalently bound retinal (see p. 358). In photosynthesis (see p. 130), reduced plastoquinone (QH2) transports protons, as well as electrons, through the membrane (Q cycle, 2). The formation of the proton gradient by the respiratory chain is also coupled to redox processes (see p. 140). In complex III, a Q,cycle is responsible for proton translocation (not shown). In cytochrome c oxidase (complex IV, 3), trans-... 

This class of enzymes [EC 3.6.1.36] (also known as the hydrogen/potassium-exchanging ATPase, the potassium-transporting ATPase, proton pump, and the gastric H+/K+ ATPase) catalyzes the hydrolysis of ATP to ADP and orthophosphate, coupled with the exchange of and ions. The gastric mucosal enzyme has been the best characterized. 

As an attempt to connect the first discussion, which was concerned with diffusion-reaction coupling, with Dr. Williams presentation of enzymes as dynamic systems, I wanted to direct attention to a number of specific systems. These are the energy-transducing proteins that couple scalar chemical reactions to vectorial flow processes. For example, I am thinking of active transport (Na-K ATPase), muscular contraction (actomyosin ATPase), and the light-driven proton pump of the well-known purple... 

Proton pump Electron transport is coupled to the phosphorylation of ADP by the transport of protons (H+) across the inner mitochon drial membrane from the matrix to the intermembrane space. This process creates across the inner mitochondrial membrane an electrical gradient (with more positive charges on the outside of the membrane than on the inside) and a pH gradient (the outside of the... 

We see that electron transfer can be accompanied by loss of a proton and that E ° may become pH dependent. (See also Eq. 16-18.) Even with cytochrome c, although there is little structural change upon electron transfer, there is an increased structural mobility in the oxidized form.156 This may be important for coupling and could also facilitate associated proton-transfer reactions. For example, it is possible that in some cytochromes the imidazole ring in the fifth coordination position may become deprotonated upon oxidation. This possibility is of special interest because cytochromes are components of proton pumps in mitochondrial membranes (Chapter 18). 

Tire most studied of all copper-containing oxidases is cytochrome c oxidase of mitochondria. This multisubunit membrane-embedded enzyme accepts four electrons from cytochrome c and uses them to reduce 02 to 2 H20. It is also a proton pump. Its structure and functions are considered in Chapter 18. However, it is appropriate to mention here that the essential catalytic centers consist of two molecules of heme a (a and a3) and three Cu+ ions. In the fully oxidized enzyme two metal centers, one Cu2+ (of the two-copper center CuA) and one Fe3+ (heme a), can be detected by EPR spectroscopy. The other Cu2+ (CuB) and heme a3 exist as an EPR-silent exchange-coupled pair just as do the two copper ions of hemocyanin and of other type 3 binuclear copper centers. 

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