Proton efflux pumps

Currently, five different molecular classes of mdr efflux pumps are known [5], While pumps of the the ATP-binding cassette (ABC) transporter superfamily are driven by ATP hydrolysis, the other four superfamilies called resistance-nodulation-division (RND), major facilitator superfamily (MFS), multidrug and toxic compound extrusion (MATE), and small multidrag resistance transporter (SMR) are driven by the proton-motive force across the cytoplasmic membrane. Usually a single pump protein is located within the cytoplasmic membrane. However, the RND-type pumps which are restricted to Gram-negative bacteria consist of two additional components, a periplasmic membrane fusion protein (MFP) which connects the efflux pump to an outer... 

Current estimates are that three protons move into the matrix through the ATP-synthase for each ATP that is synthesized. We see below that one additional proton enters the mitochondrion in connection with the uptake of ADP and Pi and export of ATP, giving a total of four protons per ATP. How does this stoichiometry relate to the P-to-O ratio When mitochondria respire and form ATP at a constant rate, protons must return to the matrix at a rate that just balances the proton efflux driven by the electron-transport reactions. Suppose that 10 protons are pumped out for each pair of electrons that traverse the respiratory chain from NADH to 02, and 4 protons move back in for each ATP molecule that is synthesized. Because the rates of proton efflux and influx must balance, 2.5 molecules of ATP (10/4) should be formed for each pair of electrons that go to 02. The P-to-O ratio thus is given by the ratio of the proton stoichiometries. If oxidation of succinate extrudes six protons per pair of electrons, the P-to-O ratio for this substrate is 6/4, or 1.5. These ratios agree with the measured P-to-O ratios for the two substrates. 

The redox system does not depend on endosomal acidification but needs TfR. Fe2Tf first binds to TfR which is located in close proximity to the proton-and electron-pumping NADHiTf oxidoreductase. The Fe—Tf bond is destabilized by proton efflux, making Fe3+ susceptible to reduction. Fe2+ is trapped by a plasma membrane binder and can be transported by a translocator [4]. As Al is a simple trivalent cation incapable of redox changes, it may be theoretically impossible that Al bound to Tf is taken up by a redox mechanism. Actually, no reports on a redox-mediated process of Al bound to Tf have been made. 

Takatsuka Y, Nikaido H. Threonine-978 in the transmembrane segment of the multidrag efflux pump AcrB of Escherichia coh is crucial for drag transport as a probable component of the proton relay network. J. Bacteriol. 2006 188 7284-7289. 

Other mechanisms conferring acetic acid resistance are also located in the cell membrane, because the toxicity of organic acids may be partly a result of a disruption of the proton motive force by acetic acid, acting as an uncoupling agent. A proton motive efflux system for acetic acid has also recently been described in A. acetii (Matsushita et al., 2005). Mutation and overexpression of the aatA gene also caused resistance to formic and propionic acids simultaneously to that of acetic acid. aatA functions as an efflux pump of acetic acid. Several transporters for monocarboxylic acids are known (Nakano, Fukaya, and Horinouchi, 2006) ... 

The membrane potential depolarization in pmal mutants could be explained if the mutant enzymes were less active in pumping protons across the membrane. This notion was supported by kinetic studies on ATP hydrolysis by these enzymes that showed small but significant decreases in Vmax (15). However, a dilemma arose when whole cell medium acidification experiments were performed, which reflect the action of the H+-ATPase in vivo. The rate of glucose-induced proton efflux by pmal mutant cells was found to be considerably better than that of wild-type cells (Figure 2). Only when high external K+ was included in the medium to minimize differences in membrane potential between mutant and wild-type cells did the activity of the... 

Fig. 10.9 Schematic representation of molecular machineries that confer acetic acid resistance in Acetobacter and Gluconacetobacter. (Schematic diagram quoted from Nakano and Fukaya 2008) THBH and phosphatidylcholine on the membrane and polysaccharide on the surface of the cells are suggested to be involved in acetic acid resistance. Acetic acid, which penetrates into the cytoplasm, is assumed to be metabolized through the TCA cycle by the actions of enzymes typical for AAB. Furthermore, intracellular acetic acid is possibly pumped out by a putative ABC transporter and proton motive force-dependent efflux pump using energy produced by ethanol oxidation or acetic acid overoxidation. Intracellular cytosolic enzymes are intrinsically resistant to low pH and are protected against denaturation by stress proteins such as molecular chaperones. ADH membrane-bound alcohol dehydrogenase, ALDH membrane-bound aldehyde dehydrogenase, CS citrate synthase, ACN aconitase, PC phosphatidylcholine...

Acetic acid efflux by transporter or pump two types of efflux system, a putative ABC transporter and a proton motive force-dependent efflux pump, function to pump out intracellular acetic acid. 

When light-driven proton pumping across the thylakoid membrane occurs, a concomitant efflux of Mg ions from vesicles into the stroma is observed. This efflux of Mg somewhat counteracts the charge accumulation due to H ... 

The proton which is generated is secreted from the osteoclasts by an ATP-dependent pump and chloride follows via a specific ion channel. Cytosolic concentration of chloride is maintained by an anion exchanger that mediates influx of chloride and efflux of bicarbonate (see Section 8.2.2 for comparison). 

Reynafarje, B., and A. L. Lehninger, The K+/site and H+/site stoichiometry of mitochondrial electron transport. J. Biol. Chem. 254 6331, 1978. Valinomycin is used to allow K+ to move inward across the inner membrane in response to the electric potential difference created by H+ efflux. The number of protons pumped out is found to be larger than previously estimated. 

Fig. 10.8. Simple biogeochemical model for metal mineral transformations in the mycorhizosphere (the roles of the plant and other microorganisms contributing to the overall process are not shown). (1) Proton-promoted (proton pump, cation-anion antiport, organic anion efflux, dissociation of organic acids) and ligand-promoted (e.g. organic adds) dissolution of metal minerals. (2) Release of anionic (e.g. phosphate) nutrients and metal cations. (3) Nutrient uptake. (4) Intra- and extracellular sequestration of toxic metals biosorption, transport, compartmentation, predpitation etc. (5) Immobilization of metals as oxalates. (6) Binding of soluble metal species to soil constituents, e.g. clay minerals, metal oxides, humic substances.

This family of transported proteins consists of proteins having approximately 110 amino acids, four TMD, and are powered by a proton motive force similar to mitochondria. These proteins must form tetramers to function as transporters. These pumps are capable of effluxing drugs, dyes, and cations. 

The last mediator of gastric secretion in the parietal cell is an H+,K+-ATPase (proton or acid pump) which is a member of the phosphorylating class of ion transport ATPases. Hydrolysis of ATP results in ion transport. This chemical reaction induces a conformational change in the protein that allows an electroneutral exchange of cytoplasmic H+ for K+. The pump is activated when associated with a potassium chloride pathway in the canalicular membrane which allows potassium chloride efflux into the extracytoplasmic space, and thus results in secretion of hydrochloric acid at the expense of ATP breakdown. The activity of the pump is determined by the access of K+ on this surface on the pump. In the absence of K+, the cycle stops at the level of the phosphoenzyme [137]. 

---