Cation-anion cotransport

Cation-anion cotransport was effected by an optically active macrotricyclic cryp-tand that carried simultaneously an alkali cation and a mandelate anion and displayed weak chiroselectivity [4.23a], as did also the transport of mandelate by an optically active acyclic ammonium cation [6.39]. Employing together a cation and an anion carrier should give rise to synergetic transport with double selection by facilitating the flow of both components of a salt (see the electron-cation symport below). Selective transport of amino acids is effected by a convergent dicarboxylic acid receptor [4.24b]. 

Both secondary active transport and positive cooperativity effects enhance carrier-mediated solute flux, in contrast to negative cooperativity and inhibition phenomena, which depress this flux. Most secondary active transport in intestinal epithelia is driven by transmembrane ion gradients in which an inorganic cation is cotransported with the solute (usually a nutrient or inorganic anion). Carriers which translocate more than one solute species in the same direction across the membrane are referred to as cotransporters. Carriers which translocate different solutes in opposite directions across the membrane are called countertransporters or exchangers (Figs. 10 and 11). 

As examples of coupled counter-transport (see Figure 13.2d) and coupled cotransport (see Figure 13.2e) the transport of titanium(lV) from low acidity (pH = 1) and high acidity ([H+] = 7 M) feed solutions, respectively using the HUM system [1,2] may be presented. The di-(2-ethyUiexyl) phosphoric acid (DEHPA) carrier reacts with Ti(IV) ion to form complexes on the feed side (see Equations 13.25 and 13.26) and reversible reactions take place on the strip side (see Equations 13.27 and 13.28). Energy for the titanium uphill transport is gained from the coupled transport of protons in the direction opposite to titanium transport from the strip to the feed solutions. In the second case (high-feed acidity), Cl anion cotransported with Ti(IV) cation in the same direction. In both cases fluxes of titanium, protons, and chlorine anion are stoichiometrically coupled. 

Energy for the titanium uphill transport is gained from the coupled transport of protons in the opposite to titanium transport from the strip to the feed solutions. In the second case (high feed acidity) Cl anion cotransported with Ti(IV) cation in the same direction. In both cases, fluxes of titanium, protons, and chlorine anion are stoichiometrically coupled. As a rule, coupled transport used combining with the facihtated transport. 

Proton or sometimes alkali metal cations are used for countertransport of cationic or cotransport of anionic solutes because of their good transport properties. It is not the case with the coupling anions. In fact, for K+ transport by 18-crown-6 in a BLM, the anion effect differs by more than 100 [96]. Many studies of the anion effect on transport efficiency have been conducted [97-100]. The effects of anion hydration free energy, anion lipophilicity, and anion interactions with solvents have been mentioned, although anion hydration free energy seems to be the major determinant of transport efficiency. For example, transport of K+ with dibenzo-18-crown-6 as a carrier, decreased in the order picrate > PFr, > CIO > IO >... 

When the transported molecule and cotransported Ion move in the same direction, the process Is called symport when they move in opposite directions, the process is called antiport (see Figure 7-2). Some cotransporters transport only positive ions (cations), while others transport only negative ions (anions). An important example of a cation cotransporter is the Na /H antiporter, which exports from cells coupled to the energetically favorable Import of Na. An example of an anion cotransporter is the AEl anion antiporter protein, which catalyzes the one-for-one exchange of Cl and HCOs across the plasma membrane. Yet other cotransporters mediate movement of both cations and anions together. In this section, we describe the operation and physiological role of several widely distributed symporters and antiporters. 

Cation transport experiments were performed in a U-tube glass cell (2.0 cm, i.d.) as reported before. The carrier in CH Cl or CHCl (12 ml) was placed in the base of the U-tube, and two aqueous phases (5 ml, each) were placed in the arms of the U-tube, floating on the membrane phase. The membrane phase was stirred constantly with a magnetic stirrer. The transport rates were calculated from the initial rates of appearance of guest cations and cotransported anion (C10 ) into the receiving aqueous phase, which were determined by means of ion selective electrodes (Orion Model 92-32 for Ba 94-82 for Pb 95-12 for NH 93-19 for K 93-81 for C10 ). 

Figure 3. Liquid Membrane for Cation Transport (M Guest Cation X"" Cotransported Anion)...

This transporter is selectively blocked by diuretic agents known as "loop" diuretics (see later in chapter). Although the Na+/K+/2Cr transporter is itself electrically neutral (two cations and two anions are cotransported), the action of the transporter contributes to excess K+ accumulation within the cell. Back diffusion of this K+ into the tubular lumen causes a lumen-positive electrical potential that provides the driving force for reabsorption of cations—including magnesium and calcium—via the paracellular pathway. Thus, inhibition of salt transport in the TAL by loop diuretics, which reduces the lumen-positive potential, causes an increase in urinary excretion of divalent cations in addition to NaCI. 

Peptide transporters of both types have been reported. Both anion and cation pumps of both types are known. Aithough most ABC famiiy members cataiyze active transport coupied to ATP hydroiysis members of the MF superfamiiy may cataiyze either mediated diffusion or active transport (coupied most often to or Na+ cotransport). A few exampies suffice to iUustrate the generai points. 

Titanium, as an example for the transport model verification, was chosen because of the extensive experimental data available on LLX and membrane separation [1,2,74—76] and of its extraction double-maximum acidity dependence phenomenon [74]. This behavior was observed for most extractant families basic (anion exchangers), neutral (complexants), and acidic (cation exchangers). So, it is possible to study both counter- and cotransport mechanisms at pH > 0.5 and [H] > 7 mol/kg feed solution acidities, respectively, using neutral (hydrophobic, hydrophilic) and ion-exchange membranes. 

Mixtures of carriers (ionic additiues). Cotransport of opposite-charged ions is the most obvious way to maintain electroneutrality, but alternative means may be explored as additives to LM. In recent years, many studies have been conducted which examine the use of anionic membrane additives for maintenance of electroneutrahty at cation transport [65, 84-89]. The anionic additives are typically fipophific carboxylic, phosphoric, or sulfonic acids. Cation or neutral macrocychc carriers coupled with anionic additives result in a synergistic transport of cations which exceeds that accomplished by each component individuaUy. This synergism was demonstrated in Ref. [90]. The authors observed a 10- to 100-fold enhancement of copper extraction. Enhanced extraction is achieved by adding the anionic group to the cation coordination macrocycle. 

Reabsorbed bile acids are transported back to the liver in the portal blood bound to albumin, where they are taken up by parenchymal cells for excretion into bile. The uptake process has been studied in isolated rat hepato-cytes (S17), the perfused rat liver (Rl), and cultured rat hepatocytes (V5), and a bile acid receptor protein has been partially characterized in liver cell membrane preparations (Al). Taken together, these studies suggest that uptake is via a coupled membrane carrier mechanism, whereby bile salt anions are cotransported with sodium cations across the liver cell sinusoidal membrane. Although the majority of bile acids are extracted from portal blood by the liver, a small fraction (less than 1% of the total bile salt pool)... 

The drug uptake (SLC) family of transporter is the largest superfamily of transporters. This family includes 31 transporters from organic anion transporter polypeptides (OATPs), organic anion transporters (OATs), organic cation transporters (OCTs), peptide cotransporters (PEPTs), and sodium-bile acid cotransporter classes. Only OATP, OAT, OCT, and PEPT are primarily involved with the transport of drugs/xenobiotics. 

ABC, ATP-binding cassette transporter superfamily ASBT, apical sodium-dependent bile salt transporter BCRP, breast cancer resistance protein BSEP, bile salt export pump MDRl, multidrug resistance MRR multidrug resistance-related protein NTCP, sodium taurocholate cotransporting polypeptide OAT, organic anion transporter OCT, organic cation transporter SLC, solute-linked carrier transporter family SLCO, solute-linked carrier organic anion transporter family. 

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