Active Transport Across the Plasma Membrane
Active transport involves expenditure of metabolic energy to move ions or other solutes across membranes against their electrochemical gradient. Its importance to cells is readily demonstrated by inhibiting the production of ATP - in such cases, the concentration of ions inside the cell soon drifts toward that of extracellular fluid and the cell dies. This effect is due to leakage of ions down their electrochemical gradient; for example, sodium leaks into the cell and potassium out of the cell. Indeed, in viable cells, a large fraction of the ATP generated is utilized in maintaining the normal electrochemical gradients of ions across the plasma membrane.
Two types of active transport are recognized. Both involve transport of solutes against an electrochemical gradient, but they differ in their source of energy:
- Primary active transport involves a carrier protein that directly hydrolyzes ATP to drive the transport process.
- Secondary active transport utilizes energy stored in electrochemical gradients of ions to drive transport - these gradients are established and maintained by carrier proteins that directly hydrolyze ATP.
Primary Active Transport
In this process, ions are moved across a cell membrane by carrier proteins that directly couple transport with hydrolysis of ATP. Such carrier proteins are usually called ATPases, although they would be better described as molecules that collect the free energy of ATP hydrolysis to move ions up an electrochemical gradient. The only substances transported by carriers that directly hydrolyze ATP are positively-charged ions - Na+, K+, Ca++ or H+.
Important examples of primary active transporters include:
- Sodium pumps or Na+-K+ ATPase are undoubtedly the premier members of this class of transport proteins. Their function is to pump 3 sodium ions out of the cell in concert with pumping 2 potassium ions into the cell, thus maintaining an intracellular environment that has low sodium and high potassium (the opposite of extracellular fluid). In most cells, one-third to one-half of the total energy expended is used to run these ion pumps. In neurons, which repeatedly gain sodium during action potentials, it's more like two-thirds of the ATP usage goes toward fueling this single transporter. Cells die rather rapidly when ATP synthesis is inhibited, and one of the major causes of this effect is the altered intracellular environmment that results when Na+-K+ pumps cannot function.
- Proton pumps function to transport H+ ions out of the cytoplasm of cells. The stomach is famous for secreting acid, and the relevant mechanism is based on a H+-K+ ATPase in the lumenal membrane of gastric parietal cells. This ion pump allows the parietal cell to secrete H+ ions against a roughly million-fold concentration gradient - truly a case of active transport! Another example of a proton pump is found in the membranes of lysosomes. These intracellular garbage disposals maintain a pH of 4.5-5.0 by pumping H+ ions from the cytoplasm into the interior of the lysosome through a carrier protein that is an ATPase.
- Calcium pumps are one mechanism cells use to shuttle calcium across cell membranes. Calcium ATPases in the plasma membrane mediate active transport of calcium out of cells, serving to maintain the normal, very low levels of free cytoplasmic calcium. Another well studied example of a calcium ATPase is found in the sarcoplasmic reticulum of muscle cells, where it serves to pump calcium from the cytoplasm into those specialized forms of endoplasmic reticulum after a period of muscle contraction. Structurally, this active transporter is very similar to the Na+-K+ ATPase.
A very interesting characteristic of all these ATP-driven ion pumps is that they are reversible. This is to say that they can be made to function as ATP synthesizing machines. If, for example, membrane vesicles containing the Ca++ ATPases described above are formed such that their inside contains high concentrations of calcium, and they are placed in an solution containing low calcium, they will synthesize ATP from added ADP and inorganic phosphorus.
The importance of this finding becomes clear when one recognizes that ATP synthesizing systems in mitochondria and chloroplasts are based on proton pumps mechanistically similar to the ATPases described here, but oriented relative to proton gradients such that they function to synthesize rather than hydrolyze ATP.
Cotransport (Secondary Active Transport)
Transport across membranes can be fueled not only by ATP, but by the energy stored in ion gradients. In such cases, the free energy released during the transport of ions down an electrochemical gradient is used to pump other ions or molecules up their electrochemical gradient. This process is called cotransport because one carrier protein mediates the transport of both species. Some cotransporters carry both solutes in the same direction (symport), while others transport one solute into the cell and the other out of the cell (antiport).
A well-studied example of symport is the cotransport of glucose and sodium into the small intestinal absorptive epithelial cell.. The carrier protein that cotransports is the sodium-dependent hexose transporter SGLUT-1. It is distributed in the apical (lumen-facing) membrane of the cells. The basolateral membranes of these cells contain Na+-K+ pumps, which actively export sodium from the cell - this maintains a low intracellular concentration of sodium and also establishes a strong electrochemical gradient of sodium across the apical membrane. This gradient of sodium provides the energy for running SGLUT-1. Cotransport is achieved through a series of conformational changes:
- a sodium ion in the intestinal lumen binds SGLUT-1, which induces a conformational change that allows a molecule of glucose to bind
- glucose binds, resulting in the carrier protein reorienting in the membrane such that the bound sodium ion and glucose face the cytoplasm
- glucose, then sodium dissociate from the carrier into the cytoplasm
- the carrier reorients back to its original position.
Two additional examples of cotransport serve to illustrate important antiporters:
- Sodium-proton cotransport involves transport of a sodium ion into the cell coupled to transport of a hydrogen ion out of the cell; both ions are transported by the same carrier protein. This process is particularly important in proximal tubules of the kidney.
- Sodium-calcium cotransport occurs in most if not all cell membranes. Sodium is carried into the cell in exchange for calcium, which is expelled from the cell.
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Last updated on November 27, 1996