At times, a large concentration of a substance is required in the intracellular fluid even though the extracellular fluid contains only a small concentration. This situation is true, for instance, for potassium ions. Conversely, it is important to keep the concentrations of other ions very low inside the cell even though their concentrations in the extracellular fluid are great. This situation is especially true for sodium ions. Neither of these two effects could occur by simple diffusion because simple diffusion eventually equilibrates concentrations on the two sides of the membrane. Instead, some energy source must cause excess movement of potassium ions to the inside of cells and excess movement of sodium ions to the outside of cells. When a cell membrane moves molecules or ions “uphill” against a concentration gradient (or “uphill” against an electrical or pressure gradient), the process is called active transport.

Different substances that are actively transported through at least some cell membranes include sodium, potassium, calcium, iron, hydrogen, chloride, iodide, and urate ions, several different sugars, and most of the amino acids.

Primary Active Transport and Secondary Active Transport. Active transport is divided into two types according to the source of the energy used to facilitate the transport: primary active transport and secondary active transport. In primary active transport, the energy is derived directly from breakdown of adenosine triphosphate (ATP) or some other high-energy phosphate compound. In secondary active transport, the energy is derived secondarily from energy that has been stored in the form of ionic concentration differences of secondary molecular or ionic substances between the two sides of a cell membrane, created originally by primary active transport. In both instances, transport depends on carrier proteins that penetrate through the cell membrane, as is true for facilitated diffusion. However, in active transport, the carrier protein functions differently from the carrier in facilitated diffusion because it is capable of imparting energy to the transported substance to move it against the electrochemical gradient. The following sections provide some examples of primary active transport and secondary active transport, with more detailed explanations of their principles of function.

PRIMARY ACTIVE TRANSPORT

Sodium-Potassium Pump Transports Sodium Ions Out of Cells and Potassium Ions Into Cells

Among the substances that are transported by primary active transport are sodium, potassium, calcium, hydro gen, chloride, and a few other ions.

The active transport mechanism that has been studied in greatest detail is the sodium-potassium (Na+-K+) pump, a transport process that pumps sodium ions outward through the cell membrane of all cells and at the same time pumps potassium ions from the outside to the inside. This pump is responsible for maintaining the sodium and potassium concentration differences across the cell mem brane, as well as for establishing a negative electrical voltage inside the cells. Indeed, Chapter 5 shows that this pump is also the basis of nerve function, transmitting nerve signals throughout the nervous system.

Figure 1 shows the basic physical components of the Na+-K+ pump. The carrier protein is a complex of two separate globular proteins—a larger one called the α subunit, with a molecular weight of about 100,000, and a smaller one called the β subunit, with a molecular weight of about 55,000. Although the function of the smaller protein is not known (except that it might anchor the protein complex in the lipid membrane), the larger protein has three specific features that are important for the functioning of the pump:

 1. It has three binding sites for sodium ions on the portion of the protein that protrudes to the inside of the cell.

 2. It has two binding sites for potassium ions on the outside.

 3. The inside portion of this protein near the sodium binding sites has adenosine triphosphatase (ATPase) activity.

Fig1. The postulated mechanism of the sodium-potassium  pump. ADP, adenosine diphosphate; ATP, adenosine triphosphate;  Pi, phosphate ion. 

When two potassium ions bind on the outside of the carrier protein and three sodium ions bind on the inside, the ATPase function of the protein becomes activated. Activation of the ATPase function leads to cleavage of one molecule of ATP, splitting it to adenosine diphosphate (ADP) and liberating a high-energy phosphate bond of energy. This liberated energy is then believed to cause a chemical and conformational change in the protein carrier molecule, extruding the three sodium ions to the outside and the two potassium ions to the inside.

As with other enzymes, the Na+-K+ ATPase pump can run in reverse. If the electrochemical gradients for Na+ and K+ are experimentally increased to the degree that the energy stored in their gradients is greater than the chemical energy of ATP hydrolysis, these ions will move down their concentration gradients and the Na+-K+ pump will synthesize ATP from ADP and phosphate. The phosphorylated form of the Na+-K+ pump, therefore, can either energy to change its conformation and pump Na+ out of the cell and K+ into the cell. The relative concentrations of ATP, ADP, and phosphate, as well as the electrochemical gradients for Na+ and K+, determine the direction of the enzyme reaction. For some cells, such as electrically active nerve cells, 60 to 70 percent of the cells’ energy requirement may be devoted to pumping Na+ out of the cell and K+ into the cell.

The Na+-K+ Pump Is Important for Controlling Cell Volume. One of the most important functions of the Na+-K+ pump is to control the volume of each cell. Without function of this pump, most cells of the body would swell until they burst. The mechanism for control ling the volume is as follows: Inside the cell are large numbers of proteins and other organic molecules that cannot escape from the cell. Most of these proteins and other organic molecules are negatively charged and therefore attract large numbers of potassium, sodium, and other positive ions as well. All these molecules and ions then cause osmosis of water to the interior of the cell. Unless this process is checked, the cell will swell indefinitely until it bursts. The normal mechanism for preventing this outcome is the Na+-K+ pump. Note again that this device pumps three Na+ ions to the outside of the cell for every two K+ ions pumped to the interior. Also, the mem brane is far less permeable to sodium ions than it is to potassium ions, and thus once the sodium ions are on the outside, they have a strong tendency to stay there. This process thus represents a net loss of ions out of the cell, which initiates osmosis of water out of the cell as well.

If a cell begins to swell for any reason, the Na+-K+ pump is automatically activated, moving still more ions to the exterior and carrying water with them. Therefore, the Na+-K+ pump performs a continual surveillance role in maintaining normal cell volume.

 Electrogenic Nature of the Na+-K+ Pump. The fact that the Na+-K+ pump moves three Na+ ions to the exterior for every two K+ ions that are moved to the interior means that a net of one positive charge is moved from the interior of the cell to the exterior for each cycle of the pump. T his action creates positivity outside the cell but results in a deficit of positive ions inside the cell; that is, it causes negativity on the inside. Therefore, the Na+-K+ pump is said to be electrogenic because it creates an electrical potential across the cell membrane. As discussed in Chapter 5, this electrical potential is a basic requirement in nerve and muscle fibers for transmitting nerve and muscle signals.

 Primary Active Transport of Calcium Ions

Another important primary active transport mechanism is the calcium pump. Calcium ions are normally maintained at an extremely low concentration in the intra cellular cytosol of virtually all cells in the body, at a concentration about 10,000 times less than that in the extracellular fluid. This level of maintenance is achieved mainly by two primary active transport calcium pumps. One, which is in the cell membrane, pumps calcium to the outside of the cell. The other pumps calcium ions into one or more of the intracellular vesicular organelles of the cell, such as the sarcoplasmic reticulum of muscle cells and the mitochondria in all cells. In each of these instances, the carrier protein penetrates the membrane and functions as an enzyme ATPase, with the same capability to cleave ATP as the ATPase of the sodium carrier protein. The difference is that this protein has a highly specific binding site for calcium instead of for sodium.

Primary Active Transport of Hydrogen Ions

 Primary active transport of hydrogen ions is important at two places in the body: (1) in the gastric glands of the stomach, and (2) in the late distal tubules and cortical collecting ducts of the kidneys.

In the gastric glands, the deep-lying parietal cells have the most potent primary active mechanism for transporting hydrogen ions of any part of the body. This mechanism is the basis for secreting hydrochloric acid in stomach digestive secretions. At the secretory ends of the gastric gland parietal cells, the hydrogen ion concentration is increased as much as a million-fold and then is released into the stomach along with chloride ions to form hydrochloric acid.

In the renal tubules, special intercalated cells found in the late distal tubules and cortical collecting ducts also transport hydrogen ions by primary active transport. In this case, large amounts of hydrogen ions are secreted from the blood into the urine for the purpose of eliminating excess hydrogen ions from the body fluids. The hydrogen ions can be secreted into the urine against a concentration gradient of about 900-fold.

 Energetics of Primary Active Transport

 The amount of energy required to transport a substance actively through a membrane is determined by how much the substance is concentrated during transport. Compared with the energy required to concentrate a sub stance 10-fold, concentrating it 100-fold requires twice as much energy, and concentrating it 1000-fold requires three times as much energy. In other words, the energy required is proportional to the logarithm of the degree that the substance is concentrated, as expressed by the following formula:

Thus, in terms of calories, the amount of energy required to concentrate 1 osmole of a substance 10-fold is about 1400 calories, whereas to concentrate it 100-fold, 2800 calories are required. One can see that the energy expenditure for concentrating substances in cells or for removing substances from cells against a concentration gradient can be tremendous. Some cells, such as those lining the renal tubules and many glandular cells, expend as much as 90 percent of their energy for this purpose alone.

SECONDARY ACTIVE TRANSPORT—CO-TRANSPORT AND COUNTER-TRANSPORT

 When sodium ions are transported out of cells by primary active transport, a large concentration gradient of sodium ions across the cell membrane usually develops, with high concentration outside the cell and low concentration inside. This gradient represents a storehouse of energy because the excess sodium outside the cell membrane is always attempting to diffuse to the interior. Under appropriate conditions, this diffusion energy of sodium can pull other substances along with the sodium through the cell membrane. This phenomenon, called co-transport, is one form of secondary active transport.

For sodium to pull another substance along with it, a coupling mechanism is required, which is achieved by means of still another carrier protein in the cell mem brane. The carrier in this instance serves as an attachment point for both the sodium ion and the substance to be co-transported. Once they both are attached, the energy gradient of the sodium ion causes both the sodium ion and the other substance to be transported together to the interior of the cell.

In counter-transport, sodium ions again attempt to diffuse to the interior of the cell because of their large concentration gradient. However, this time, the substance to be transported is on the inside of the cell and must be transported to the outside. Therefore, the sodium ion binds to the carrier protein where it projects to the exterior surface of the membrane, while the substance to be counter-transported binds to the interior projection of the carrier protein. Once both have become bound, a conformational change occurs, and energy released by the action of the sodium ion moving to the interior causes the other substance to move to the exterior.

Co-Transport of Glucose and Amino Acids Along with Sodium Ions

 Glucose and many amino acids are transported into most cells against large concentration gradients; the mechanism of this action is entirely by co-transport, as shown in Figure 2 Note that the transport carrier protein has two binding sites on its exterior side, one for sodium and one for glucose. Also, the concentration of sodium ions is high on the outside and low inside, which provides energy for the transport. A special property of the trans port protein is that a conformational change to allow sodium movement to the interior will not occur until a glucose molecule also attaches. When they both become attached, the conformational change takes place, and the sodium and glucose are transported to the inside of the cell at the same time. Hence, this is a sodium-glucose co-transport mechanism. Sodium-glucose co-transporters are especially important mechanisms in transporting glucose across renal and intestinal epithelial cells, as dis cussed in Chapters 28 and 66.

Fig2. The postulated mechanism for sodium co-transport of  glucose. 

Sodium co-transport of the amino acids occurs in the same manner as for glucose, except that it uses a different set of transport proteins. At least five amino acid trans port proteins have been identified, each of which is responsible for transporting one subset of amino acids with specific molecular characteristics.

Sodium co-transport of glucose and amino acids occurs especially through the epithelial cells of the intestinal tract and the renal tubules of the kidneys to pro mote absorption of these substances into the blood. This process will be discussed in later chapters.

Other important co-transport mechanisms in at least some cells include co-transport of chloride, iodine, iron, and urate ions.

 Sodium Counter-Transport of Calcium and Hydrogen Ions

Two especially important counter-transport mechanisms (i.e., transport in a direction opposite to the primary ion) are sodium-calcium counter-transport and sodium hydrogen counter-transport (Figure 3).

Fig3. Sodium counter-transport of calcium and hydrogen  ions.

Sodium-calcium counter-transport occurs through all or almost all cell membranes, with sodium ions moving to the interior and calcium ions to the exterior; both are bound to the same transport protein in a counter-transport mode. This mechanism is in addition to primary active transport of calcium that occurs in some cells.

Sodium-hydrogen counter-transport occurs in several tissues. An especially important example is in the proxi mal tubules of the kidneys, where sodium ions move from the lumen of the tubule to the interior of the tubular cell while hydrogen ions are counter-transported into the tubule lumen. As a mechanism for concentrating hydro gen ions, counter-transport is not nearly as powerful as the primary active transport of hydrogen ions that occurs in the more distal renal tubules, but it can transport extremely large numbers of hydrogen ions, thus making it a key to hydrogen ion control in the body fluids, as dis cussed in detail in Chapter 31.

ACTIVE TRANSPORT THROUGH CELLULAR SHEETS

At many places in the body, substances must be trans ported all the way through a cellular sheet instead of simply through the cell membrane. Transport of this type occurs through the (1) intestinal epithelium, (2) epithelium of the renal tubules, (3) epithelium of all exocrine glands, (4) epithelium of the gallbladder, and (5) mem brane of the choroid plexus of the brain, along with other membranes.

The basic mechanism for transport of a substance through a cellular sheet is (1) active transport through the cell membrane on one side of the transporting cells in the sheet, and then (2) either simple diffusion or facilitated diffusion through the membrane on the opposite side of the cell.

Figure 4 shows a mechanism for transport of sodium ions through the epithelial sheet of the intestines, gallbladder, and renal tubules. This figure shows that the epithelial cells are connected together tightly at the luminal pole by means of junctions. The brush border on the luminal surfaces of the cells is permeable to both sodium ions and water. Therefore, sodium and water diffuse readily from the lumen into the interior of the cell. T hen, at the basal and lateral membranes of the cells, sodium ions are actively transported into the extracellular fluid of the surrounding connective tissue and blood vessels. This action creates a high sodium ion concentration gradient across these membranes, which in turn causes osmosis of water as well. Thus, active transport of sodium ions at the basolateral sides of the epithelial cells results in transport not only of sodium ions but also of water.

Fig4. The basic mechanism of active transport across a layer  of cells.

It is through these mechanisms that almost all nutrients, ions, and other substances are absorbed into the blood from the intestine. These mechanisms are also the way the same substances are reabsorbed from the glomerular filtrate by the renal tubules.

Numerous examples of the different types of trans port discussed in this chapter are provided throughout this text.

مواضيع ذات صلة

MEASURING THE MEMBRANE POTENTIAL

BASIC PHYSICS OF MEMBRANE POTENTIALS

The Cell Membrane Consists of A Lipid Bilayer With Cell Membrane Transport Proteins

Apoptosis—Programmed Cell Death

Cilia and Ciliary Movements

تركيب الخلية Structure of the cell

LYSOSOMES

السيطرة على انقسام الخلية

الظاهرة الأسموزية

طرق انتقال المواد من وإلى الخلية من خلال الغشاء

انتقال المواد الغذائية من وإلى الخلية عبر غشاء الخلية

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