Carrier Proteins and Active Membrane Transport
The process by which a carrier protein transfers a solute molecule across the lipid bilayer resembles anenzyme-substrate reaction, and in many ways carriers behave like enzymes. In contrast to ordinary enzyme-substrate reactions, however, the transported solute is not covalently modified by the carrier protein, but instead is delivered unchanged to the other side of the membrane.
Each type of carrier protein has one or more specific binding sites for its solute (substrate). It transfers the solute across the lipid bilayer by undergoing reversible conformational changes that alternately expose the solute-binding site first on one side of the membrane and then on the other. A schematic model of how such a carrier protein is thought to operate is shown in Figure 11-6. When the carrier is saturated (that is, when all solute-binding sites are occupied), the rate of transport is maximal. This rate, referred to as Vmax, is characteristic of the specific carrier and reflects the rate with which the carrier can flip between its two conformational states. In addition, each transporter protein has a characteristic binding constant for its solute,Km, equal to the concentration of solute when the transport rate is half its maximum value (Figure 11-7). As with enzymes, the binding of solute can be blocked specifically by either competitive inhibitors (which compete for the same binding site and may or may not be transported by the carrier) or noncompetitive inhibitors (which bind elsewhere and specifically alter the structure of the carrier).

Figure 11-6A model of how a conformational change in a carrier protein could mediate the passive transport of a solute
The carrier protein shown can exist in two conformational states: in state A, the binding sites for solute are exposed on the outside of the lipid bilayer; in state B, the same sites are exposed on the other side of the bilayer. The transition between the two states can occur randomly. It is completely reversible and does not depend on whether the solute binding site is occupied. Therefore, if the solute concentration is higher on the outside of the bilayer, more solute binds to the carrier protein in the A conformationthan in the B conformation, and there is a net transport of solute down its concentration gradient (or, if the solute is an ion, down its electrochemical gradient). http://www.ncbi.nlm.nih.gov/books/NBK26896/figure/A2000/?report=objectonly As we discuss below, it requires only a relatively minor modification of the model shown in Figure 11-6 to link the carrier protein to a source of energy in order to pump a solute uphill against its electrochemical gradient. Cells carry out such active transport in three main ways (Figure 11-8):

Three ways of driving active transport. The actively transported molecule is shown in yellow, and the energy source is shown in red.
1.Coupled carriers couple the uphill transport of one solute across the membrane to the downhill transport of another.
2.ATP-driven pumps couple uphill transport to the hydrolysis of ATP.
3.Light-driven pumps, which are found mainly in bacterial cells, couple uphill transport to an input of energy from light, as with bacterio-rhodopsin (discussed in Chapter 10).
Amino acid sequence comparisons suggest that, in many cases, there are strong similarities in molecular design between carrier proteins that mediate active transport and those that mediate passive transport. Some bacterial carriers, for example, which use the energy stored in the H+ gradient across the plasma membrane to drive the active uptake of various sugars, are structurally similar to the carriers that mediate passive glucosetransport into most animal cells. This suggests an evolutionary relationship between various carrier proteins; and, given the importance of small metabolites and sugars as an energy source, it is not surprising that the superfamily of carriers is an ancient one.
We begin our discussion of active transport by considering carrier proteins that are driven by ion gradients. These proteins have a crucial role in the transport of small metabolites across membranes in all cells. We then discuss ATP-driven pumps, including the Na+ pump that is found in the plasma membrane of almost all cells.
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Active Transport Can Be Driven by Ion Gradients
Some carrier proteins simply transport a single solute from one side of the membrane to the other at a ratedetermined as above by V max and Km; they are called uniporters. Others, with more complex kinetics, function as coupled carriers, in which the transfer of one solute strictly depends on the transport of a second. Coupled transport involves either the simultaneous transfer of a second solute in the same direction, performed by symporters, or the transfer of a second solute in the opposite direction, performed by antiporters (Figure 11-9).

Figure 11-9Three types of carrier-mediated transport
This schematic diagram shows carrier proteins functioning as uniporters, symporters, and antiporters.

The tight coupling between the transport of two solutes allows these carriers to harvest the energy stored in theelectrochemical gradient of one solute, typically an ion, to transport the other. In this way, the free energy released during the movement of an inorganic ion down an electrochemical gradient is used as the driving force to pump other solutes uphill, against their electrochemical gradient. This principle can work in either direction; some coupled carriers function as symporters, others as antiporters. In the plasma membrane of animal cells, Na+ is the usual co-transported ion whose electrochemical gradient provides a large driving force for the active transport of a second molecule. The Na+ that enters the cell during transport is subsequently pumped out by an ATP-driven Na+ pump in the plasma membrane (as we discuss later), which, by maintaining the Na+gradient, indirectly drives the transport. (For this reason ion-driven carriers are said to mediate secondary active transport, whereas ATP-driven carriers are said to mediate primary active transport.) Intestinal and kidney epithelial cells, for example, contain a variety of symport systems that are driven by the Na+ gradient across the plasma membrane; each system is specific for importing a small group of related sugars or amino acids into the cell. In these systems, the solute and Na+ bind to different sites on a carrier protein. Because the Na+ tends to move into the cell down its electrochemical gradient, the sugar or amino acid is, in a sense, “dragged” into the cell with it. The greater the electrochemical gradient for Na+, the greater the rate of solute entry; conversely, if the Na+ concentration in the extracellular fluid is reduced, solute transport decreases (Figure 11-10).

Figure 11-10One way in which a glucose carrier can be driven by a Na+ gradient
As in the model shown in Figure 11-6, the carrier oscillates between two alternate states, A and B. In the A state, the protein is open to the extracellular space; in the B state, it is open to the cytosol. Binding of Na+ and glucose is cooperative—that is, the binding of either ligand induces a conformational change that greatly increases the protein's affinity for the other ligand. Since the Na+ concentration is much higher in the extracellular space than in the cytosol, glucose is more likely to bind to the carrier in the A state. Therefore, both Na+ and glucose enter the cell (via an A → B transition) much more often than they leave it (via a B → A transition). The overall result is the net transport of both Na+ and glucose into the cell. Note that because the binding is cooperative, if one of the two solutes is missing, the other fails to bind to the carrier. Thus, the carrier undergoes a conformational switch between the two states only if both solutes or neither are bound. In bacteria and yeasts, as well as in many membrane-enclosed organelles of animal cells, most active transport systems driven by ion gradients depend on H+ rather than Na+ gradients, reflecting the predominance of H+ pumps and the virtual absence of Na+ pumps in these membranes. The active transport of many sugars and amino acids into bacterial cells, for example, is driven by the electrochemical H+ gradient across theplasma membrane. One well-studied H+ -driven symport is lactose permease, which transports lactose across the plasma membrane of E. coli. Although the folded structure of the permease is unknown, biophysical studies and extensive analyses of mutant proteins have led to a detailed model of how the symport works. The permease consists of 12 loosely packed transmembrane α helices. During the transport cycle, some of the helices undergo sliding motions that cause them to tilt. These motions alternately open and close a crevice between the helices, exposing the binding sites for the solutes lactose and H+, first on one side of the membrane and then on the other (Figure 11-11).

Figure 11-11A model for the molecular mechanism of action of the bacterial lactose permease
(A) A view from the cytosol of the proposed arrangement of the 12 predicted transmembrane helices in the membrane. The loops that connect the helices on either side of the membrane are omitted for clarity. A glutamic acid on helix X binds H+, and amino acids contributed by helices IV and V bind lactose. (B) During a transport cycle, the carrier flips between two conformational states: in one, the H+ -and lactose-binding sites are accessible to the extracellular space (1 and 2); in the other, they are exposed to the cytosol (3 and 4). Unloading of the solutes on the cytosolic face (3 → 4) is favored because the lactose-binding site is partly disrupted and a positive charge contributed by an arginine on helix IX displaces the H+ from the glutamic acid on helix X. (A, adapted from H.R. Kaback and J. Wu, Accts. Chem. Res. 32:805-813, 1999.)

Secondary Active Transport
Secondary active transport is a form of active transport across a biological membrane in which a transporter protein couples the movement of an ion (typically Na+ or H+) downits electrochemical gradient to the uphill movement of another molecule or ion against a concentration/electrochemical gradient. Thus, energy stored in the electrochemical gradient of an ion is used to drive the transport of another solute against a concentration or electrochemical gradient. The ion moving down its electrochemical gradient is referred to as the driving ion because it is movement of this ion that drives the uphill movement of another ion/molecule (driven ion/molecule). Secondary active transport is also commonly referred to as ion-coupled transport and, in fact, coupling between the driving and driven species is obligatory. That is to say that both the driving and driven species must be bound to the transporter for translocation across the membrane to occur. Unlike in primary active transport in which ATP hydrolysis provides the free energy needed to move solutes against a concentration gradient, in secondary active transport, the free energy needed to perform active transport is provided by the concentration gradient of the driving ion. To call this process secondary active transport is appropriate since the existence and maintenance of the concentration gradient of the driving ion is accomplished by primary active transporters (i.e., pumps). Sodium serves as the driving ion in many (but not all) secondary active transporters located in the plasma membrane of various cells. This is appropriate as there is a steep Na+ concentration gradient across the plasma membrane that is maintained by the Na+/K+/ATPase. In mammals, the extracellular Na+ concentration ([Na+]o) is around 145 mM and the intracellular Na+concentration ([Na+]i) is around 15 mM. The free energy stored in this gradient is used by Na+-coupled transporters to drive the uphill movement of substrates.
Two types of secondary active transport: Cotransport and Exchange
Two variations of secondary active transport exist: cotransport (also known as symport) and exchange (also known as antiport). The transport proteins responsible for secondary active transport are referred to as secondary active transporters and are specifically referred to as cotransporters (also known as symporters) and exchangers (also known as antiporters). Cotransport and cotransporters are also commonly written as co-transport, and co-transporters, respectively. Sodium is the driving ion for many cotransporters and exchanger and, therefore, these transport proteins may also be referred to as sodium-coupled cotransporters. Similarly, there are many examples of proton-coupled cotransporters and exchangers. Figures 1 and 2 provide a summary of these secondary active transport processes.

Figure 1. Secondary active transport.
In secondary active transport, the movement of a driving ion down an electrochemical gradient is used to drive the uphill transport of another ion/molecule against a concentration or electrochemical gradient. Two types of secondary active transport processes exist: cotransport (also known as symport) and exchange (also known as antiport). In cotransport, the direction of transport is the same for both the driving ion and driven molecule/ion, whereas in exchange, the driving ion and driven ion/molecule are transported in opposite directions. X and Y represent transporter substrates.Na+, sodium; K+, potassium; ATP, adenosine triphosphate; ADP, adenosine diphosphate; Pi, inorganic phosphate.
In cotransport, the direction of transport is the same for both the driving ion and driven ion/molecule. For example, the Na+/glucose cotransporter (SGLT1), found in the small intestine and kidney proximal tubules, simultaneously transports 2 Na+ ions and 1 glucose molecule into the cell across the plasma membrane. In contrast, in exchange, the driving ion and driven ion/molecule move in opposite directions. For example, the Na+/Ca2+ exchanger (NCX), found in cardiac muscle cells and elsewhere in the body, transports 3 Na+ ions into the cell in exchange for 1 Ca2+ion transported out of the cell. Not all cotransporters utilize Na+ as the driving ion. Some use an existing proton electrochemical gradient. For example, the H+/oligopeptide transporter (PepT), found in the small intestine, couples the downhill movement of H+ across the plasma membrane to the uphill transport of dipeptides and tripeptides into the cell against a concentration gradient.
Not all secondary active transporters are found in the plasma membrane. For example, H+/neurotransmitter exchangers, found in the membrane of synaptic vesicles in axon terminals, utilize the proton electrochemical gradient across the vesicle membrane to drive the uphill transport of neurotransmitter into the vesicle (Fig. 2). In all cases, the electrochemical gradient of the driving ion is maintained by primary active transporters. The Na+ gradient across the plasma membrane is maintained by the Na+/K+/ATPase and the proton gradient across the synaptic vesicle membrane is maintained by the H+/ATPase.

Figure 2. Secondary active transport across vesicular membranes.
Secondary active transporters may also be localized to the membrane of internal organelles. For example, H+/neurotransmitter exchangers use the H+electrochemical gradient (proton electromotive force) established by the V-type H+/ATPase to drive neurotransmitter molecules against a concentration gradient into the lumen of synaptic vesicles. NT, neurotransmitter; H+, proton; ATP, adenosine triphosphate; ADP, adenosine diphosphate; Pi, inorganic phosphate.
Transport coupling stoichiometry determines the effectiveness of substrate transport against a concentration gradient
For both cotransporters and exchangers, the effectiveness of the transport process can be defined by theconcentrative capacity of the transport process. Concentrative capacity is a measure of how well the driven ion/molecule is concentrated against a concentration gradient. For example, for the Na+/glucose cotransporter, concentrative capacity can be expressed as the ratio of intracellular to extracellular glucose concentration ([Glucose]i/[Glucose]o). This ratio indicates how well the Na+/glucose cotransporter can concentrate glucose inside of the cell against a concentration gradient. Concentrative capacity is strictly related to the ion/substrate coupling stoichiometry of the transporter per transport cycle. For example, the coupling stoichiometry of the intestinal Na+/glucose cotransporter is 2 Na+ ions to 1 glucose molecule per transport cycle. That is to say that there is thermodynamic coupling between Na+ and glucose cotransport. For any given transporter, the coupling stoichiometry is usually a fixed ratio. A higher ion/substrate coupling ratio (e.g., 3:1 vs. 2:1) leads to a significantly higher concentrative capacity of transport.
Cotransporters and exchangers may be electrogenic or electroneutral
A consequence of the ion/substrate coupling ratio is that the activity of some cotransporters and exchangers leads to the translocation of net charge across the membrane. A transporter that leads to the net translocation of charge across the membrane is said to be electrogenic. For example, with a coupling stoichiometry of 2 Na+ ions to 1 glucose/galactose molecule, Na+/glucose cotransport by SGLT1 represents an electrogenic process. Such charge movements across the membrane lead to small electrical currents and, therefore, electrophysiological methods may be used to measure the activity of electrogenic transporters. When no net charge is transported across the membrane per transport cycle, the process is said to be electroneutral. Figures 3 and 4 provide a few examples of cotransporter proteins, and Fig. 5 provides examples of exchanger proteins.
Direction of transport is determined by the electrochemical or concentration gradient of the driving ion/species
While the physiological concentration gradient of the driving ion normally determines the direction of transport in cotransporters and exchangers, under experimental conditions, cotransporters and exchangers may work in reverse if the concentration gradient of the driving ion is reversed. For example, if the intracellular and extracellular concentrations of Na+ are experimentally reversed, the Na+/glucose transporter would utilize this gradient to transport 2 Na+ ions and 1 glucose molecule out of the cell (provided that the glucose substrate is present inside of the cell). Generally, the coupling stoichiometry of transport is the same whether the transporter works in the forward or reverse mode. Moreover, if the experimental conditions are designed to create a sufficiently high concentration of the transported substrate, the transporter can then utilize this artificial concentration gradient to drive the uphill transport of the normally designated driving ion! For example, leaving the normal inwardly-directed Na+ electrochemical gradient intact, if the cytoplasmic glucose concentration is experimentally made to be very high, then glucose would in fact act as the driving species to drive SGLT-mediated cotranslocation of 2 Na+ ions and 1 glucose molecule out of the cell! Therefore, secondary active transporters can be thought of as thermodynamic machines that respond to the concentration gradients of the driving ion as well as the driven ion/molecule. Physiologically, the driven ion/molecule is moved against a concentration gradient, but experimentally, its concentration gradient can be defined to make it the driving ion/molecule! This point is described later when examining the thermodynamics of the Na+/glucose cotransporter.
Examples of cotransporters
A few examples of cotransporter proteins are shown in Figures 3 and 4. Please note that this is only a partial list of cotransporters.

Figure 3. Examples of cotransport proteins.
Cotransport proteins (cotransporters or symporters) are found in many different cells and tissues and perform a variety of important physiological functions. Six examples are shown here. See text for details. Na+, sodium; K+, potassium; Cl-, chloride; I-, iodide; Pi, inorganic phosphate.
The Na+/glucose cotransporter (SGLT1) is found in the apical membrane of epithelial cells of the small intestine and renal proximal tubules. It utilizes the Na+ electrochemical gradient to drive the uphill transport of glucose into the cell. As mentioned above, the ion/substrate coupling stoichiometry of SGLT is 2 Na+ ions 1 glucose molecule (Fig. 3). Therefore, SGLT1 is an electrogenic transporter. In addition to glucose, SGLT1 recognizes galactose as a substrate. Its function is crucial to dietary glucose and galactose absorption in the small intestine and reabsorption of filtered glucose and galactose in the proximal tubule of kidney nephrons.
The Na+/phosphate cotransporter (NaPi) is found in the apical membrane of epithelial cells of the small intestine and renal proximal tubules. It utilizes the Na+ electrochemical gradient to drive the uphill transport of inorganic phosphate (Pi) into the cell. For every transport cycle, NaPi (IIa and IIb) couples the inward translocation of 3 Na+ ions and 1 divalent Pi (HPO42-) (Fig. 3). Thus, NaPi types IIa and IIb are electrogenic transporters. A third type, NaPi-IIc (not shown here), is electroneutral with a coupling stoichiometry of 2 Na+ to 1 divalent Pi (HPO42-).
The Na+/I- symporter (NIS) is responsible for the accumulation of iodide by the thyroid gland. It is localized to the basolateral membrane of thyroid follicular cells and co-translocates 2 Na+ ions and 1 I- ion per transport cycle (Fig. 3). NIS is also found in other tissues such as in the mammary glands, where it functions to transport iodide into the nursing mother's milk.
The Na+/K+/2Cl- cotransporter (NKCC), the Na+/Cl- cotransporter (NCC), as well as the K+/Cl- cotransporter (KCC) belong to the same family of transporters (Fig. 3). The Na+/K+/2Cl- cotransporter (NKCC) utilizes the Na+ electrochemical gradient to drive the inward cotranslocation of Na+, K+, and Cl- with a 1 Na+ : 1 K+ : 2 Cl- stoichiometry. Among other places, NKCC is found in the apical membrane of the thick ascending limb of the loop of Henle, where it performs an important role in urine concentration. The so-called "loop diuretics" block the activity of NKCC. The Na+/Cl- cotransporter (NCC) utilizes the Na+ electrochemical gradient to drive Cl-transport into the cell with a 1 Na+ : 1 Cl- coupling stoichiometry. NCC is found in the apical membrane of the epithelial cells of kidney nephron distal tubules and, in fact, is the target of thizaide diuretics. The K+/Cl- cotransporter (KCC) cotranslocates 1 K+ and 1 Cl- out of the cell per transport cycle. Here, the driving ion is K+. Remember that the activity of the Na+/K+/ATPase creates a large outwardly directed K+ electrochemical gradient ([K+]i = 150 mM and [K+]o = 4 mM). As apparent from the coupling stoichiometry ratios shown in Fig. 3, NKCC, NCC, and KCC are all electroneutral cotransporters.

Figure 4. Additional examples of cotransport proteins.
Six additional examples of cotransporters are shown. See text for details. R-COO- represents monocarboxylates such as lactate, pyruvate, acetoacetate, and β-hydroxybutyrate. Na+, sodium; H+, proton; Cl-, chloride; HCO3-, bicarbonate; GABA, γ-aminobutyric acid.
The transporter for the inhibitory neurotransmitter γ-aminobutyric acid (GABA) belongs to a large family of Na+- and Cl--coupled transporters. The GABA transporter (GAT) regulates the basal concentration of GABA in the nervous system and, in addition, regulates the concentration and lifetime of GABA in the synaptic cleft. The GABA transporters couple the inward translocation of both Na+ and Cl- to the simultaneous inward translocation of GABA with a coupling stoichiometry of 2 Na+ : 1 Cl- : 1 GABA (Fig. 4). Thus, the GABA transporters are electrogenic. Other transporters that belong to this family are transporters for the neurotransmitters serotonin, dopamine, and norepinephrine, as well as transporters for the osmolytes betaine and taurine.
The H+/monocarboxylate cotransporter (MCT) recognizes monocarboxylates such as lactate, pyruvate, acetoacetate, and β-hydroxybutyrate. It is a proton-driven transporter with a coupling stoichiometry of 1 H+ : 1 monocarboxylate and, thus, MCT is an electroneutral transporter (Fig. 4). The direction of transport is governed by the prevailing proton gradient.
The H+/oligopeptide transporter (PepT) is located in the apical membrane of the small intestine epithelial cells and renal proximal tubules. It couples the downhill movement of 1 H+ to the uphill movement of 1 dipeptide or 1 tripeptide (Fig. 4). In addition, PepT serves as the entry route for peptidomimetic drugs such as β-lactam antibiotics. Stomach emptying of acidic chyme into the early regions of the small intestine creates an acidic environment with a favorable transmembrane proton gradient for PepT-mediated transport of di/tripeptides. PepT is thought to be the dominant player in nitrogen absorption in the small intestine and nitrogen reabsorption in the kidney tubules.
Sodium-coupled bicarbonate cotransporters (NBC) perform important acid-base balance functions. Both electroneutral (NBCn) and electrogenic (NBCe) isoforms have been identified (Fig. 4). Remarkably, the NBCs belong to the same family as Cl-/bicarbonate exchagers discussed below (AE). For the electrogenic isoforms, the coupling stoichiometry appears to vary depending on the tissue in which the transporter is expressed. The direction of transport may be inward or outward. For example, NBCe1 located in the basolateral membrane of kidney proximal tubules, mediates the outward translocation of 1 Na+ ion and 3 HCO3- ions into the interstitial fluid, where the reabsorbed bicarbonate is returned to the circulation by entering the peritubular capillaries. Thus, NBCe1 plays a crucial role in renal bicarbonate reabsorption.
Examples of exchangers

Figure 5. Examples of exchangers.
Exchangers (also known as antiporters) are found in many different cells and tissues and perform a variety of important physiological functions. Three examples are shown here. See text for details. Na+, sodium; Ca2+, calcium;H+, proton; Cl-, chloride; HCO3-, bicarbonate.
The Na+/Ca2+ exchanger (NCX) is ubiquitously found in many cells and tissues and plays an important role in cytoplasmic Ca2+ homeostasis. It couples the inward movement of 3 Na+ ions down the Na+ electrochemical gradient to the uphill movement of 1 Ca2+ ion against a very steep electrochemical gradient (Fig. 5). Remember that resting Ca2+ concentration values in the cytoplasm and extracellular fluid are 70 nM and 2 mM, respectively. NCX is electrogenic.
A ubiquitously found exchanger that plays a key role in the regulation of cytoplasmic pH is the Na+/H+ exchanger (NHE). Here again, the Na+ electrochemical gradient is utilized by the exchanger to extrude H+ from the cell with a 1 Na+ : 1 H+ coupling stoichiometry (Fig. 5). Thus, NHE is electroneutral.
Another exchanger that is widely distributed is the Cl-/bicarbonate exchanger (also referred to as anion exchanger or AE). The coupling stoichiometry of transport is 1 Cl- to 1 HCO3- and, therefore, the exchanger is electroneutral (Fig. 5). As mentioned above, these exchangers belong to the same family as Na+-coupled bicarbonate cotransporters (NBC). The direction of transport by the Cl-/bicarbonate exchanger is governed by the concentration gradients of Cl- and bicarbonate. For example, in red blood cells (erythrocytes) travelling in systemic capillaries, excess production of bicarbonate in the cytoplasm (as a result of CO2 hydration reaction catalyzed by carbonic anhydrase) drives the outward translocation of HCO3- in exchange for inward translocation of Cl-. When the red cells pass through the lung capillaries, the direction of transport is reversed such that inward translocation of HCO3- is coupled to outward translocation of Cl-. The HCO3- that enters the cells ultimately gives rise to CO2 (catalyzed by carbonic anhydrase), which then leaves the cell and ultimately the capillaries to enter the air-filled alveoli of the lungs, where it is then exhaled into the atmosphere.
Cotransporters and exchangers represent many gene families in the human genome
The examples of cotransporters and exchangers given above do not take into consideration that many of the transporters discussed have multiple isoforms and that features such as tissue localization, coupling stoichiometry, substrate specificity, etc. may vary among the isoforms. Moreover, there may be differences among ortholog transporters (i.e., species differences such as human versus rat or mouse). For a complete list of secondary active transporters found in the human genome, please visit the Human Genome Organization (http://www.hugo-international.org/) nomenclature page (http://www.genenames.org/).
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Primary and Secondary Active Transport

The active transport of molecules across cell membranes is one of the major factors on molecular level for keeping homeostasis within the body. This kind of transport requires energy as they transport molecules against their concentration gradient. It is divided into two types according to the source of energy used, called primary active transport and secondary active transport. In primary active transport, the energy is derived directly from the breakdown of ATP. In the secondary active transport, the energy is derived secondarily from energy that has been stored in the form of ionic concentration differences between the two sides of a membrane.
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Cell Membrane
The cell membrane consists of a lipid bilayer including a large amount of protein molecules. These are considered as integral or peripheral membrane proteins. The lipid bilayer constitutes a barrier for the movement of different substances. However, some substances, especially lipid-soluble substances, are still able to pass this lipid bilayer through diffusion. The membrane proteins show different properties for the transport of substances. Their molecular structures interrupt the continuity of the lipid bilayer and thereby constitute an alternative pathway through the cell membrane. Hence the vast majority of the membrane proteins are regarded as transport proteins. They play a crucial role in keeping the ion concentration intracellular and extracellular on a physiological level. The way how transportation is achieved differs among three groups of transport proteins. * Large pores, consisting of several protein subunits, that allow the bulk flow of water, ions and larger molecules down their chemical concentration gradients (facilitated diffusion). No additional metabolic activity is required hereby. * ATP-dependent ion pumps is the usage of direct or indirect metabolic energy to move molecules against its electrochemical gradient. * Specialized ion channels that only allow the passage of particular ions across the membrane.
The substances that are transported across the membrane can cross alone, along with other molecules or in exchange: * Uniporters, that move one type of molecule in one direction * Symporters, that move several molecules in one direction * Antiporters, that move different molecules in opposite directions.
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Primary Active Transport
Primary active transport utilizes energy in form of ATP to transport molecules across a membrane against their concentration gradient. Therefore, all groups of ATP-powered pumps contain one or more binding sites for ATP, which are always present on the cytosolic face of the membrane.
Based on the transport mechanism as well as genetic and structural homology, there are considered four classes of ATP-dependent ion pumps: * P-class pumps * F-class pumps * V-class pumps * ABC superfamily
The P-, F- and V-classes only transport ions, while the ABC superfamily also transports small molecules.
The energy expended by cells to maintain the concentration gradients of some ions across the plasma and intracellular membranes is considerable: * In kidney cells, up to 25 % of the ATP produced by the cell is used for ion transport; * In electrically active nerve cells, 60 -70 % of the cells’ energy requirement may be devoted to pumping Na+ out of the cell and K+ into the cell.
Example: Na+/K+ pump
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Secondary Active Transport
Secondary active transport, is transport of molecules across the cell membrane utilizing energy in other forms than ATP. This energy comes from the electrochemical gradient created by pumping ions out of the cell. This Co-Transport can be either via antiport or symport.
The formation of the electrochemical gradient which enables the co-transport is made by the primary active transport of Na+. Na+ is actively transport out of the cell creating a much higher concentration extracellular than intracellular. This gradient becomes energy as the excess Sodium is constantly trying to diffuse to the interior. This mechanism provides the energy needed for the co-transport of other ions and substances.
(GUYTON, Arthur C – HALL, John E. Textbook of Medical Physiology. 11th edition. 2006. ISBN 0-7216-0240-1. WARD, Jeremy P.T, et al. Physiology at a Glance. 2nd edition. 2008. ISBN 978-1-4051-7723-8.)