Differences between active and passive transport

According to Textbook of Biochemistry with Clinical Correlations, 3e, by T.M. Devlin (New York: Wiley-Liss,1992), p. 226, in forms of passive transport, like diffusion, molecules move across the membrane down the concentration gradient. In active transport, molecules move against this gradient, that is, from an area of low concentration to an area of high concentration of the solute.

There are two types of active transport: primary and secondary. In primary active transport, the cell uses energy that it gets from the hydrolysis of ATP, from radiant energy, or from electron transport. One example of a protein that transports molecules across a cell membrane against the concentration gradient is the Na⁺-K⁺ pump, which can transport glycoproteins and many drugs across the cell membrane.

In secondary active transport, cells use potential energy created by an electrical gradient across the membrane, created either by an ion gradient or a transmembrane potential. Even though proteins that hydrolize ATP are not involved here, this is still active transport, since molecules are moving against the concentration gradient.

The key to understanding the difference between passive and active transport, no matter what the mechanism is, is that active transport moves molecules against the concentration gradient. Passive transport moves molecules down the concentration gradient, but some forms of passive transport require energy input. It’s not the input of energy that defines the mode of transport, but the concentration gradient.

We need to make an example out of the Na⁺-K⁺ pump to describe one way the cell harnesses energy for this active transport of molecules across the plasma membrane.

The direct use of ATP in active transport

The protein known as the sodium-potassium pump is an interstitial membrane protein that spans the entire bilayer, with parts exposed on the intracellular side and parts exposed on the extracellular side. This protein uses about 23 percent of all the ATP a cell makes through metabolic pathways, when that cell is not dividing (dividing takes a lot of energy). Therefore, more energy is spent in maintaining the concentrations of sodium and potassium ions inside the cell than in any other activity except cell division. Indeed, the homeostatic role of this pump is so critical that it is the major user of ATP in red blood cells in most species (source: DeWeer, P. Renal Na,K-ATPase. In: Seldin DW, Giebisch G., editors. The Kidney: Physiology and Pathophysiology. Raven Publishing; New York: 1985. pp. 31–55).

Most cells in an animal have a lower concentration of sodium and a higher concentration of potassium inside the cell than outside. Without active transport, the concentration of sodium and potassium would eventually reach an equilibrium, and the cell would cease to function, since this gradient drives much of the cell’s activity.

Because the sodium-potassium pump moves both sodium and potassium against their concentration gradients (it pumps three sodium ions out of the cell for every two potassium ions it pumps in), energy is required as input to this process. This energy comes from adenosine triphosphate (ATP).

Step 1. Na⁺ ions bind to the cytoplasmic side of the sodium potassium pump. This bond causes the sodium-potassium pump protein to change shape, known as changing its conformation.

Step 2. Pump protein binds a molecule of ATP, and the protein serves as a catalyst to break the ATP up into adenosine diphosphate (ADP) and an inorganic phospate ion (P_i).

Even though the ADP molecule is released after the ATP is broken apart, the phosphate remains bound to the protein, and the sodium-potassium pump protein is now said to be phosphorylated.

Step 3. Protein changes shape again. The phosphorylation causes a second conformation change in the sodium-potassium pump protein. As it twists and folds itself all over again, the three sodium ions bound in Step 1 above move over to the extracellular side of the protein. The change in shape also causes the protein to have a much lower affinity for the sodium ions, and they are released into the extracellular matrix.

Step 4. K⁺ ions bind to the pump, doing so from the extracellular side, because the new conformation of the pump has a very high affinity for potassium ions. The binding occurs almost immediately following the release of the sodium ions, but not to the same site.

Step 5. The phosphate is released from the inside of the pump protein, because the binding of the potassium ion in Step 4 causes a third conformational change in the protein. The new conformation has a low affinity for phosphate.

Step 6. Finally, the K⁺ ions are released to the inside of the cell. The key here is that the protein reverts to its original shape once the phosphate is released. This conformation causes the two potassium ions to move to the inside and release from the protein. As noted in Step 1, this original conformation has a high affinity for sodium ions on the intracellular side, and when sodium ions bind, the cycle repeats.

Source: Peter H. Raven. Biology, 7e (Boston: McGraw Hill, 2005), p. 121.

Glucose-Sodium Symport

Animal cells can never get enough glucose: it is the molecule needed for cellular respiration, which produces all the ATP in the cell and is needed for all sorts of cell functions. However, the concentration of glucose in the extracellular fluid is almost always less than the glucose concentration inside the cell. The cell, therefore, needs to transport glucose into the cell against its concentration gradient. Anytime you have a molecule moving across the membrane against its concentration gradient, active transport is involved, by definition.

But unlike the sodium-potassium pump, which binds ATP and harnesses the energy directly from ATP, the transport protein that brings glucose into the cell against its concentration gradient does not bind ATP at all. It gets its energy from another source entirely:

As specified above, much of the cell’s energy is expended in maintaining a higher concentration of sodium outside the cell than inside. Did you ever wonder why this gradient was so important that cells would spend a full one-quarter of their energy just to maintain the concentration gradient for the sodium ion? The key to this question is glucose, along with other important molecules (neurotransmitters, etc.) for which this gradient drives cotransport across a membrane.

Another interstitial protein in the cell membrane is the glucose-sodium coupled transport protein. This protein has a conformation initially in which both glucose and sodium ions bind to the extracellular side. Because the concentration of sodium is much higher outside the cell than inside, the sodium naturally moves down its concentration gradient, into the cell.

Instead of requiring energy as input to drive this movement, as with the sodium-potassium pump, the process of sodium moving down its concentration gradient actually gives off energy. This energy can be harnessed by the coupled transport protein, which then has enough energy to move the glucose molecule into the cell, up its concentration gradient.

This type of transport, sometimes called symport or coupled transport, is active by definition, since it is moving glucose against its concentration gradient. All forms of active transport require energy as input, but coupled transport gets the energy not from the breaking up of an ATP molecule, but from harnessing the energy released when a completely different molecule (or ion, in this case) moves down its concentration gradient.

Summary

In conclusion, there are two types of transport of molecules across a semipermeable membrane: passive, which includes diffusion and osmosis, in which molecules move down their concentration gradient, from an area of higher concentration to an area of lower concentration; and active, which includes (a) transport processes that use the energy from ATP directly, and (b) processes, usually called coupled transport, that use the energy from a concentration gradient or other potential energy across the membrane to move molecules against their concentration gradient.

With coupled transport, both molecules (the one being actively transported and the one that provides the energy for the transport) often move in the same direction, as with the active transport of glucose, coupled to the movement of sodium ions. This type of coupled transport is called “symport,” as opposed to “antiport,” in which the coupled ions or molecules move in opposite directions across the membrane. There are plenty of examples of both types of coupled transport.

The transport proteins in the membrane have sites that are very specific to the particular molecules being actively transported. This means, the protein that couples glucose transport to the sodium concentration gradient would not work for sucrose or some other sugar.

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