Symport examples

The gradients of H, Na, and other cations and anions established by ATPases and other energy sources can be used for secondary active transport of various substrates. The best-understood systems use Na or gradients to transport amino acids and sugars in certain cells. Many of these systems operate as symports, with the ion and the transported amino acid or sugar moving in the same direction (that is, into the cell). In antiport processes, the ion and the other transported species move in opposite directions. (For example, the anion transporter of erythrocytes is an antiport.) Proton symport proteins are used by E. coU and other bacteria to accumulate lactose, arabinose, ribose, and a variety of amino acids. E. coli also possesses Na -symport systems for melibiose as well as for glutamate and other amino acids. 

Transport systems can be described in a functional sense according to the number of molecules moved and the direction of movement (Figure 41-10) or according to whether movement is toward or away from equilibrium. A uniport system moves one type of molecule bidirectionally. In cotransport systems, the transfer of one solute depends upon the stoichiometric simultaneous or sequential transfer of another solute. A symport moves these solutes in the same direction. Examples are the proton-sugar transporter in bacteria and the Na+ -sugar transporters (for glucose and certain other sugars) and Na -amino acid transporters in mammalian cells. Antiport systems move two molecules in opposite directions (eg, Na in and Ca out). 

The difference in the hydrogen ion electrochemical potential, formed in bacteria similarly as in mitochondria, can be used not only for synthesis of ATP but also for the electrogenic (connected with net charge transfer) symport of sugars and amino acids, for the electroneutral symport of some anions and for the sodium ion/hydrogen ion antiport, which, for example, maintains a low Na+ activity in the cells of the bacterium Escherichia coli. 

Examples of such intra cellular membrane transport mechanisms include the transfer of pyruvate, the symport (exchange) mechanism of ADP and ATP and the malate-oxaloacetate shuttle, all of which operate across the mitochondrial membranes. Compartmentalization also allows the physical separation of metabolically opposed pathways. For example, in eukaryotes, the synthesis of fatty acids (anabolic) occurs in the cytosol whilst [3 oxidation (catabolic) occurs within the mitochondria. 

Several symport proteins have been identified in the luminal and basolateral surfaces of the proximal tubule cells, each with a specific transport function. For example, mechanisms exist for transport of (i) neutral amino acids, except glycine, (ii) glycine alone, (iii) acidic amino acids (glutamate and aspartate), (iv) basic amino acids... 

Co-transport, also known as symport, is the transport of one compound that is obligatorily linked to that of another. An example is the transport of glucose and Na ions (see below). In counter-transport, also known as antiport, the transporter transports one compound in one direction and... 

Figure 9.13 Examples of mitochondrial transport systems for anions. 0 The anb port system transfers malate into but oxo-glutarate out of the mitochondrion. The symport system transfers both pyruvate and protons into the mitochondrion across the inner membrane. Both transport processes are electroneutral.

Some cells couple the pure transport forms discussed on p. 218—i.e., passive transport (1) and active transport (2)—and use this mechanism to take up metabolites. In secondary active transport (3), which is used for example by epithelial cells in the small intestine and kidney to take up glucose and amino acids, there is a symport (S) located on the luminal side of the membrane, which takes up the metabolite M together with an Na" ion. An ATP-dependent Na transporter (Na /lC ATPase see p. 350) on the other side keeps the intracellular Na+ concentration low and thus indirectly drives the uptake of M. Finally, a uniport (U) releases M into the blood. 

The perchlorate ion of potassium perchlorate, KCIO4, is a competitive inhibitor of thyroidal 1 transport via the Sodium Iodide Symporter (NIS).This drug can cause fatal aplastic anemia and gastric ulcers and is now rarely used. If administered with careful supervision, in limited low doses and for only brief periods, serious toxic effects can be avoided. The compound is especially effective in treating iodine-induced hyperthyroidism, which may occur, for example, in patients treated with the antiar-rhythmic compound amiodarone. Perchlorate ion can also be used in a diagnostic test of 1 incorporation into Tg, the so-called perchlorate discharge test. 

As described in the paragraphs above, conclusions on a direct effect of any of these ions should be drawn with caution, since a change in the concentration of any of these may activate a regulatory mechanism to compensate for the change, for example the Na+/H+ exchanger, the Na+/HCC>3 symport or the Na+/Ca2+-exchange mechanism. 

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... 

Active transport of a solute against a concentration gradient also can be driven by a flow of an ion down its concentration gradient. Table 17.6 lists some of the active-transport systems that operate in this way. In some cases, the ion moves across the membrane in the opposite direction to the primary substrate (antiport) in others, the two species move in the same direction (symport). Many eukaryotic cells take up neutral amino acids by coupling this uptake to the inward movement of Na+ (see fig. 17.26c). As we discussed previously, Na+ influx is downhill thermodynamically because the Na+-K+ pump keeps the intracellular concentration of Na+ lower than the extracellular concentration and sets up a favorable electric potential difference across the membrane. Another example is the /3-galactosidc transport system of E. coli, which couples uptake of lactose to the inward flow of protons (see fig. 17.26Proton influx is downhill because electron-transfer reactions (or,... 

Historically important as an example of flux coupling, and one that was investigated in detail becoming a paradigm for coupled transport, was the sodium coupled glucose transport system of the small intestine and kidney (see below). This was a symport (or co-transport) rather than an antiport, normally carrying glucose into the cell coupled to a flow of sodium ions in the same direction. 

Most mitochondria contain an active H+/phosphate symport protein containing a sulfhydryl group essential for its translocator activity, (a) How could this translocator complicate measurements of the H+/0 ratio (as in Example 14.9), and (b) how could the presence of the sulfhydryl group be used to obviate these complications ... 

Isotonic water resorption in the ephitelium is an example for the secondary active transport. Water and sodium ions are symported from the blood isotonically (i.e., against their concentration gradients) and there is no transport of either in the absence of the other. 

Thiazides. Diuretics that act on the distal convoluted tubule and inhibit the sodium chloride symporter, leading to retention of water in the urine. An example is hydrochlorothiazide. 

Secondary transporters are ancient molecular machines, common today in bacteria and archaea as well as in eukaryotes. For example, approximately 160 (of approximately 4000) proteins encoded by the E. coli genome appear to be secondary transporters. Sequence comparison and hydropathy analysis suggest that members of the largest family have 12 transmemhrane helices that appear to have arisen by duplication and fusion of a membrane protein with 6 transmemhrane helices. Included in this family is the lactose permease of E. coli. This symporter uses the H+ gradient... 

Figure 13.11. Action of Lactose Permease. Lactose permease pumps lactose into bacterial cells by drawing on the proton-motive force. The binding sites evert when a lactose molecule (L) and a proton (H+) are bound to external sites. After these species are released inside the cell, the binding sites again evert to complete the transport cycle. Lactose permease is an example of a symporter.

An example of leaks can be found in the case of a solute symport system, for instance the proton-sugar symport in bacteria. In that case a protein specifically catalyzes the transport of protons and sugar across the membrane, by being able to... 

Cotransport of sugars with H+ is especially common in bacteria but also occurs in eukaryotes. For example, the alga chlorella employs hexose / symporters. 2 xhe most investigated cotransporter is probably the lactose (lac) permease from E. coU which enables E. coli to take up lactose and other P-galactosides from very dilute solutions. 23-436 a... 

Many transmembrane transporter proteins, termed secondary transporters, use the discharge of an ionic gradient to power the uphill translocation of a solute molecule across membranes. Couphng solute movement to ion transport enables these secondary transporters to concentrate solutes by a factor of 10 with a solute flux 10 faster than by simple diffusion. We have already encountered the co-transport of leucine and Na+ by LeuT, but there are many other examples. Sugars and amino acids can be transported into cells by Na+-dependent symports. Dietary glucose is concentrated in the epithelial cells of the small intestine by a Na -dependent symport, and is then... 

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). 

---