Antiport carrier systems

Owing to observations on certain competitive and reciprocal antiport relations between sugar and amino acid transport, Alvarado and Crane and Alvarado have recently postulated a new polyfunctional, mobile carrier system. involved in the uphill transport of sugars, neutral amino acids and basic amino acids in the small intestine that consists of a mosaic of fixed, specific membrane sites which acquire mobility as a result of deformations of the mobile membrane resulting in local, transient engagements of the two protein surfaces, thus allowing bound substrates to be alternately exposed to the extra- and intercellular fluids. ... 

The melibiose carrier MelB of E. coli is a well-studied sodium symport system. This carrier is of special interest, because it can also use protons or lithium ions for cotransport. The projection structure of MelB has been solved at 8 A resolution [107]. The 12 TM helices are arranged in an asymmetrical pattern similar to the previously solved structure of NhaA, which, however, follows an antiport mechanism (Na+ ions out of the cell and H+ into the cell). 

The Na ion concentration within the cell is maintained low, due to activity of an enzyme known as the Na+/K+ ATPase. This enzyme/carrier is present in the plasma membrane. It is an antiport system that transports three Na+ ions out of the cell and two K+ ions into the cell, for each molecule of ATP that is hydrolysed (Figure 5.10). It is responsible for maintaining a low Na+ ion concentration but a high K+ ion concentration within the ceU. Its constant activity in many it not all cells requires constant ATP hydrolysis, which accounts for more than 10% of the resting energy expenditure of an adult. 

Transporters, particularly those carrying nonlipophilic species across biomembranes or model membranes, can be regarded as vectorial catalysts (and are also called carriers, translocators, permeases, pumps, and ports [e.g., symports and antiports]). Many specialized approaches and techniques have been developed to characterize such systems. This is reflected by the fact that there are currently twenty-three volumes in the Methods in Enzymology series (vols. 21,22,52-56,81,88,96-98,125-127,156-157, 171-174, and 191-192) devoted to biomembranes and their constituent proteins. Chapters in each of these volumes will be of interest to those investigating transport kinetics. Other volumes are devoted to ion channels (207), membrane fusion techniques (220 and 221), lipids (14, 35, 71, and 72), plant cell membranes (148), and a volume on the reconstitution of intracellular transport (219). See Ion Pumps... 

There are, however, various types of active transport systems, involving protein carriers and known as uniports, symports, and antiports as indicated in Figure 3.7. Thus, symports and antiports involve the transport of two different molecules in either the same or a different direction. Uniports are carrier proteins, which actively or passively (see section "Facilitated Diffusion") transport one molecule through the membrane. Active transport requires a source of energy, usually ATP, which is hydrolyzed by the carrier protein, or the cotransport of ions such as Na+ or H+ down their electrochemical gradients. The transport proteins usually seem to traverse the lipid bilayer and appear to function like membrane-bound enzymes. Thus, the protein carrier has a specific binding site for the solute or solutes to be transferred. For example, with the Na+/K+ ATPase antiport, the solute (Na+) binds to the carrier on one side of... 

Electron-anion antiport has been realized, for instance with redox active carriers such as ferrocene derivatives [6.51a] or alkylviologens [6.44-6.46,6.51b] via ferricinium or reduced viologen species, respectively. The latter have been used extensively in light-driven systems and in studies on solar energy conversion [6.44-6.46],... 

Fatty acids are generated cytoplasmically while acetyl-CoA is made in the mitochondrion by pyruvate dehydrogenase.This implies that a shuttle system must exist to get the acetyl-CoA or its equivalent out of the mitochondrion. The shuttle system operates in the following way Acetyl-CoA is first converted to citrate by citrate synthase in the TCA-cycle reaction. Then citrate is transferred out of the mitochondrion by either of two carriers, driven by the electroos-motic gradient either a citrate/phosphate antiport or a citrate/malate antiport as shown in Figure 2-2. 

The carrier-mediated uptake of p-aminohippuric acid (PAH) into BBMV (Figure 7) and PAH accumulation by renal cortical slices [69,77] were also significantly reduced by CPH treatment (1200 mg/kg/d for 3d). Furthermore, the transport of other cephalosporins across the renal brush border membrane is also affected by CPH-treatment the uptake of cephalexin and cefotiam into BBMV was greatly reduced whereas the uptake of CPH remained unaffected [77]. Secretion of cephalosporins across the brush border membrane is assumed to occur by the PAH-system as well as by the organic cation/H+-antiporter [127,133]. Reabsorption of many cephalosporins is performed by the dipeptide transport system [69, 133]. The unaffected uptake of CPH into BBMV from CPH-treated rats indicates that CPH is transported by a system different from the... 

Transport of many compounds including drugs across cell membranes is mediated by membrane proteins called carrier proteins or channel proteins. Some of these proteins transport only one substrate molecule at a time across the membrane (uniport systems), while others act as cotransport systems (Figure 9.4). Depending on the direction of the second substrate, the proteins are also called symporters or antiporters, for example, Na /glucose cotransporter, H " /peptide cotransporter, or Na /K antiporter (—Na /K -ATPase). 

The mechanism of the competitive pertraction system (CPS) is presented schematically in Fig. 5.4 together with the compartmental model necessary for constructing the reaction-diffusion network. The simple flat-layered bulk liquid membrane of the thickness En and interface area S separates the two reservoirs (f, feed and s, stripping) containing transported divalent cations A2+ and B2+ (most frequently Zn2+ and Cu2+ or Ca2+ and Mg2+) and/or antiported univalent cations H+. At any time of pertraction t, their concentrations are [A]f, [B]f, and [H]f and [A]s, [Bj, and [H]s, for the feed and stripping solution, respectively. The hydrophobic liquid membrane contains a carrier of total concentration [C]. Its main property is the ability to react reversibly with cations at respective reaction zone and to diffuse throughout the liquid membrane phase. 

Mitchell [7] visualized three different systems for facilitated secondary transport. Uniport only one solute is translocated by the carrier protein. Symport two or more different solutes are translocated in the same direction by the carrier protein. Antiport two or more different solutes are translocated by one carrier in opposite directions. 

A carrier which transports a single molecule in one direction is called a uniport system. Alternatively, a carrier may carry two molecules simultaneously in the same direction, i.e. a symport system. TTiirdly, a carrier may exchange one molecule for another and therefore transport them in opposite directions, i.e an antiport system (Figure 9.4). 

Most ATP-requiring reactions occur in the cytosol and produce ADP and orthophosphate. Since most ATP is formed by mitochondrial oxidative phosphorylation (in appropriate cells) from ADP and orthophosphate, these molecules must traverse the inner membrane. ATP and ADP are translocated by the specific adenine-nucleotide-transport system. This antiport system is widely distributed in the membrane and exchanges one mitochondrial ATP for one cytoplasmic ADP. The carrier selectively binds and transports ADP inwards and ATP outwards. The phosphate enters the mitochondrion via a different antiport system, the phosphate carrier, which exchanges it for a hydroxyl ion. 

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