5.3 Active Transport

Electrochemical Gradient

We have discussed simple concentration gradients—a substance's differential concentrations across a space or a membrane—but in living systems, gradients are more complex. Because ions move into and out of cells and because cells contain proteins that do not move across the membrane and are mostly negatively charged, there is also an electrical gradient, a difference of charge, across the plasma membrane. The interior of living cells is electrically negative with respect to the extracellular fluid in which they are bathed, and at the same time, cells have higher concentrations of potassium (K⁺) and lower concentrations of sodium (Na⁺) than the extracellular fluid. Thus in a living cell, the concentration gradient of Na⁺ tends to drive it into the cell, and its electrical gradient (a positive ion) also drives it inward to the negatively charged interior. However, the situation is more complex for other elements such as potassium. The electrical gradient of K⁺, a positive ion, also drives it into the cell, but the concentration gradient of K⁺ drives K⁺ out of the cell (Figure 5.16). We call the combined concentration gradient and electrical charge that affects an ion its electrochemical gradient.

Visual Connection

Figure 5.16 Electrochemical gradients arise from the combined effects of concentration gradients and electrical gradients. Na⁺ ions are at higher concentration outside the cell, and K⁺ ions are at higher concentration inside of the cell, and yet the inside of the cell has negative net charge compared to the other side of the membrane. This is due to the presence of K⁺ binding proteins and other negatively charged molecules. The difference in electrical charges attracts the positively charged Na ions toward the inside of the cell, the electrical gradient, while the K ions tend to flow through K channels toward the outside of the cell due to the concentration difference, the concentration gradient. Structures labeled A represent proteins. (credit: “Synaptitude”/Wikimedia Commons)

Injecting a potassium solution into a person’s blood is lethal. This is how capital punishment and euthanasia subjects die. Why do you think a potassium solution injection is lethal?

Figure 5.17 Proton Gradient provides energy for a secondary active transporter. The proton pump creates an electrochemical gradient of protons (hydrogen ions, H+) using ATP to drive primary active transport. This gradient allows for cotransport/secondary transport of sucrose against its concentration gradient as protons come down their concentration gradient via their membrane cotransporter protein. Credit: Rao, A. Tag, A. and Ryan, K. Department of Biology, Texas A&M University.

Carrier Proteins for Active Transport

An important membrane adaptation for active transport is the presence of specific carrier proteins or pumps to facilitate movement: there are three protein types or transporters (Figure 5.18). A uniporter carries one specific ion or molecule. A symporter carries two different ions or molecules, both in the same direction. An antiporter also carries two different ions or molecules, but in different directions. All of these transporters can also transport small, uncharged organic molecules like glucose. These three types of carrier proteins are also in facilitated diffusion, but they do not require ATP to work in that process. Some examples of pumps for active transport are Na⁺-K⁺ ATPase, which carries sodium and potassium ions, and H⁺-K⁺ ATPase, which carries hydrogen and potassium ions. Both of these are antiporter carrier proteins. Two other carrier proteins are Ca²⁺ ATPase and H⁺ ATPase, which carry only calcium and only hydrogen ions, respectively. Both are pumps.

Figure 5.18 A uniporter carries one molecule or ion. A symporter carries two different molecules or ions, both in the same direction. An antiporter also carries two different molecules or ions, but in different directions. (credit: modification of work by “Lupask”/Wikimedia Commons)

Primary Active Transport

The primary active transport that functions with the active transport of sodium and potassium allows secondary active transport to occur. The second transport method is still active because it depends on using energy as does primary transport (Figure 5.19).

Figure 5.19 The sodium-potassium pump is an example of primary active transport that moves ions, sodium and potassium ions in this instance, across a membrane against their concentration gradients. The energy is provided by the hydrolysis of ATP. Three sodium ions are moved out of the cell for every 2 potassium ions that are brought into the cell. This creates an electrochemical gradient that is crucial for living cells. Credit: Rao, A., Ryan, K. and Fletcher, S. Department of Biology, Texas A&M University.

One of the most important pumps in animal cells is the sodium-potassium pump (Na⁺-K⁺ ATPase), which maintains the electrochemical gradient (and the correct concentrations of Na⁺ and K⁺) in living cells. The sodium-potassium pump moves K⁺ into the cell while moving Na⁺ out at the same time, at a ratio of three Na⁺ for every two K⁺ ions moved in. The Na⁺-K⁺ ATPase exists in two forms, depending on its orientation to the cell's interior or exterior and its affinity for either sodium or potassium ions. The process consists of the following six steps.

1. With the enzyme oriented towards the cell's interior, the carrier has a high affinity for sodium ions. Three ions bind to the protein.
2. The protein carrier hydrolyzes ATP and a low-energy phosphate group attaches to it.
3. As a result, the carrier changes shape and reorients itself towards the membrane's exterior. The protein’s affinity for sodium decreases and the three sodium ions leave the carrier.
4. The shape change increases the carrier’s affinity for potassium ions, and two such ions attach to the protein. Subsequently, the low-energy phosphate group detaches from the carrier.
5. With the phosphate group removed and potassium ions attached, the carrier protein repositions itself towards the cell's interior.
6. The carrier protein, in its new configuration, has a decreased affinity for potassium, and the two ions moves into the cytoplasm. The protein now has a higher affinity for sodium ions, and the process starts again.

Several things have happened as a result of this process. At this point, there are more sodium ions outside the cell than inside and more potassium ions inside than out. For every three sodium ions that move out, two potassium ions move in. This results in the interior being slightly more negative relative to the exterior. This difference in charge is important in creating the conditions necessary for the secondary process. The sodium-potassium pump is, therefore, an electrogenic pump (a pump that creates a charge imbalance), creating an electrical imbalance across the membrane and contributing to the membrane potential.

Secondary Active Transport (Co-transport)

Secondary active transport uses the kinetic energy of the sodium ions to bring other compounds, against their concentration gradient into the cell. As sodium ion concentrations build outside of the plasma membrane because of the primary active transport process, this creates an electrochemical gradient. If a channel protein exists and is open, the sodium ions will move down its concentration gradient across the membrane. This movement transports other substances that must be attached to the same transport protein in order for the sodium ions to move across the membrane (Figure 5.20). Many amino acids, as well as glucose, enter a cell this way. This secondary process also stores high-energy hydrogen ions in the mitochondria of plant and animal cells in order to produce ATP. The potential energy that accumulates in the stored hydrogen ions translates into kinetic energy as the ions surge through the channel protein ATP synthase, and that energy then converts ADP into ATP.

Visual Connection

Figure 5.20 An electrochemical gradient (Na⁺ concentration - green), is generated by primary active transport. The energy stored in the Na⁺ gradient provides the energy to move other substances against their concentration gradients (Glucose - blue), a process called co-transport or secondary active transport. Credit: Rao, A., Ryan, K., Tag, A. and Fletcher, S. Department of Biology, Texas A&M University.

If the pH outside the cell decreases, would you expect the amount of amino acids transported into the cell to increase or decrease?