Proton co-transporters

The pyruvate, glutamate and phosphate transporters catalyze net uptake and release of their substrates with stoicheiometric amounts of protons [6]. Early evidence for the electroneutrality of the process was the good inverse correlation between the H gradient across the mitochondrial membrane and the gradients of these permeant anions, especially at equilibrium and at low metabolite concentrations [96,97]. At equilibrium the rate of inward transport should equal the rate of efflux and the distribution of permeant anion should be proportional to the A pH since  

It has been shown experimentally that relationship (4) is maintained whether the internal or external pH is varied in order to change A pH. Relationship (4) could also be derived by assuming that the free acid is completely permeable and the anion impermeable to the membrane. At equilibrium the concentration of free acid should be equal inside and out, and the amount of internal and external anions determined by pK and ApH. 

However, since the proportion of most metabohtes present as free acid at pH 7 is low, it is likely that the carriers have separate binding sites for protons and anions. The relationships between proton concentrations, substrate concentrations and rates of transport have been examined in order to gain insight into the molecular mechanisms of transport for the glutamate, pyruvate and phosphate carriers. 

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F. Malek and D. A. Baker, Proton Co-transport of Sugars in Phloem Loading, Planta 135, 297-299 (1977). 

Wu, X., L. R. Whitfield, and B. H. Stewart. Atorvastatin transport in the Caco-2 cell model contributions of P-glycoprotein and the proton-monocarboxylic acid co-transporter. Pharm. Res. 2000, 17, 209-215. 

The proton-motive Q-cycle model, put forward by Mitchell (references 80 and 81) and by Trumpower and co-workers, is invoked in the following manner (1) One electron is transferred from ubiquinol (ubiquinol oxidized to ubisemi-quinone see Figure 7.27) to the Rieske [2Fe-2S] center at the Qo site, the site nearest the intermembrane space or p side (2) this electron can leave the bci complex via an attached cytochrome c or be transferred to cytochrome Ci (3) the reactive ubisemiquinone reduces the low-potential heme bL located closer to the membrane s intermembrane (p) side (4) reduced heme bL quickly transfers an electron to high-potential heme bn near the membrane s matrix side and (5) ubiquinone or ubisemiquinone oxidizes the reduced bn at the Qi site nearest the matrix or n side. Proton translocation results from the deprotonation of ubiquinol at the Qo site and protonation of ubisemiquinone at the Qi site. Ubiquinol generated at the Qi site is reoxidized at the Qo site (see Figure 7.27). Additional protons are transported across the membrane from the matrix (see Figure 7.26 illustrating a similar process for cytochrome b(6)f). The overall reaction can be written... 

The first step is the activation, i.e., protonation of the carrier. The active proto-nated carrier can react with cephalosporin anion (P ) to form a complex AHP which is soluble in organic phase. The transport of anion from one phase to another requires the co-transport of cation (H+). The reaction is instantaneous and the mass transport of the ionic species controls the reaction rate. 

Facilitated transport of penicilHn-G in a SLM system using tetrabutyl ammonium hydrogen sulfate and various amines as carriers and dichloromethane, butyl acetate, etc., as the solvents has been reported [57,58]. Tertiary and secondary amines were found to be more efficient carriers in view of their easy accessibility for back extraction, the extraction being faciUtated by co-transport of a proton. The effects of flow rates, carrier concentrations, initial penicilHn-G concentration, and pH of feed and stripping phases on transport rate of penicillin-G was investigated. Under optimized pH conditions, i. e., extraction at pH 6.0-6.5 and re-extraction at pH 7.0, no decomposition of peniciUin-G occurred. The same SLM system has been applied for selective separation of penicilHn-G from a mixture containing phenyl acetic acid with a maximum separation factor of 1.8 under a liquid membrane diffusion controlled mechanism [59]. Tsikas et al. [60] studied the combined extraction of peniciUin-G and enzymatic hydrolysis of 6-aminopenicillanic acid (6-APA) in a hollow fiber carrier (Amberlite LA-2) mediated SLM system. 

The co-transport of di- and tripeptides with protons has been well studied in the small intestine and kidneys, and showed enhanced absorption of peptides by the... 

GMO photo current PET across membrane is accompanied by co-transport of proton, which is also carried by photosensitizer 97... 

A potassium chloride co-transporter must be closely related to the H /K -ATPase during proton secretion. Potassium and chloride ions move across the apical membrane together with secreted protons Figure 4.1) [15-17]. Potassiiun is recycled while hydrochloric acid of the gastric juice is formed by chloride ions together with the secreted protons. Stimulation of gastric acid secretion across the apical membrane may predominantly reflect the activation or insertion of an active potassium chloride co-transporter rather than direct activation of HVK -ATPase [1]. 

The co-transport of water with protons (the so-called electro-osmotic drag) is to some extent unavoidable, at least in aqueous media, due to the fact that protons do not migrate through the membrane as such but as part of protonated clusters I D, 110, (see below). Water transport should, however, be reduced as much as possible for several reasons ... 

Sundaram, U., Wisel, S. and Coon, S. (2005) Mechanism of inhibition of proton dipeptide co-transport during chronic enteritis in the mammalian small intestine. Biochimica et Biophysica Acta, 1714 (2), 134-140. 

Studies on sugar and amino acid uptake by L. donovani promastigotes revealed that addition of D-glucose or L-proline caused a rapid influx of protons into these cells, indicating that both substrates are co-transported with protons (52). This active transport system involves a proton-motive force (pmf)-driven mechanism which requires the maintenance of a proton electrochemical gradient. Such a gradient is composed of the chemical gradient (ApH) and the membrane potential (Ai/ ) (52). 

Studies on the uptake of Ni by M. bryantii have demonstrated the presence of a highly specific uptake system with = 3.1 p,mol dm. This pathway was not affected by high levels of other metal cations, including Mg but with the exception of Co. Transport of Ni is coupled to movement of protons. Usually uptake of Ni into bacteria occurs by the transport process for magnesium, not surprisingly in view of their similar ionic radii. It is appropriate, therefore, that an organism such as M. bryantii which has a specific requirement for Ni should have a specific transport system for its uptake. 

Gale, Smith and co-workers have developed prodigiosin mimics based on amidopyrroles in order to co-transport hydrochloride acid across a vesicle membrane. The inclusion of the protonatable imidazole group allows the receptor to carry the proton of the acid and in addition, once protonated, provides an extra hydrogen bond donor group to bind the chloride within the cleft [51]. 

One research area of particular interest is new proton-conducting solid polymer electrolyte membrane (PEM) materials possessing the desired properties, namely, (1) high proton conductanee at high temperature (up to 120°C), (2) effectively no co-transport of molecular species with proton, (3) reduction of electrode overpotential, and (4) good mechanical strength and chemical stability. 

Together with substrates such as glucose and amino acids, thus providing a mechanism for net accumulation of these substrates, driven by the sodium gradient, which in turn has been created by the proton gradient produced by the hydrolysis of ATE This is a co-transport mechanism as the sodium ions and substrates travel in the same direction across the cell membrane ... 

Isotherms for the interfacial tension at an aqueous/organic interface show that the new di-(p-alkylphenyl)phosphoric acids 3-6 adsorb at the interface stronger than do commercially available DEHPA (1) or Cyanex 272(2). From the interfacial fluxes for single transition metal cation species transport across a bulk kerosene membrane, the following selectivity orders were derived Zn(II) > Cu(II) > Co(II) > Ni(II) for 1, 5, and 6 Cu(II) > Zn(II) > CoJI) > Ni(II) for 2 and 3 and Cu(II), Zn(II) > CoJI) > Ni(II) for 4. Similar selectivity orders were observed in competitive transport of these transition metal cations across emulsion liquid membranes in which a high utilization degree of the carrier was demonstrated. The di-(p-alkylphenyl)phosphoric acids 3-6 are found to be efficient carriers for proton-coupled transport of transition metal cations from a weakly acidic aqueous source phase across an emulsion liquid... 

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