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CHAPTER 11

Transmembrane Transport of Ions and Small Molecules

In all cells, the plasma membrane forms the barrier that separates the cytoplasm from the exterior environment, thus defining a cell’s physical and chemical boundaries. By preventing the unimpeded movement of molecules and ions into and out of the cell, the plasma membrane maintains essential differences between the composition of the extracellular fluid and that of the cytosol. For example, the concentration of sodium chloride (NaCl) in the blood and extracellular fluids of animals is generally above 150 mM, similar to the ~450 mM Na⁺ found in the seawater, in which all cells are thought to have evolved. In contrast, the sodium ion (Na⁺) concentration in the cytosol is tenfold lower, about 15 mM, while the potassium ion (K⁺) concentration is higher in the cytosol than outside.

Organelle membranes, which separate the cytosol from the interior of the organelle, also form permeability barriers. For example, the proton concentration in the lysosome interior, pH 5, is about a hundredfold greater than that of the cytosol, and many specific metabolites accumulate at higher concentrations in the interior of other organelles, such as the endoplasmic reticulum or the Golgi complex, than in the cytosol.

All cellular membranes, both plasma membranes and organelle membranes, consist of a bilayer of phospholipids in which other lipids and specific types of proteins are embedded. It is this combination of lipids and proteins that gives cellular membranes their distinctive permeability qualities. If cellular membranes were pure phospholipid bilayers (see Figure 10-4), they would be excellent chemical barriers, impermeable to virtually all ions, amino acids, sugars, and other water-soluble molecules. In fact, only a few gases and small, uncharged, water-soluble molecules can readily diffuse across a pure phospholipid bilayer (Figure 11-1). But cellular membranes must serve not only as barriers, but also as conduits, selectively transporting molecules and ions from one side of the membrane to the other. Energy-rich glucose, for example, must be imported into the cell, and wastes must be shipped out.

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Movement of virtually all small molecules and ions across cellular membranes is mediated by membrane transport proteins—integral membrane proteins with multiple transmembrane domains embedded in cellular membranes. These membrane-spanning proteins act variously as shuttles, channels, or pumps for transporting molecules and ions through a membrane’s hydrophobic interior. In some cases, molecules or ions are transported from a higher to a lower concentration, a thermodynamically favored process powered by an increase in entropy. Examples include the transport of water or glucose from the blood into most body cells. In other cases, molecules or ions must be pumped from a lower to a higher concentration, a thermodynamically unfavorable process that can occur only when an external source of energy is available to push the molecules “uphill” against a concentration gradient. An example of such a process is the concentration of protons within lysosomes to generate a low pH in the lumen. Often the required energy is provided by mechanistic coupling of the energy-releasing hydrolysis of the terminal phosphoanhydride bond in ATP with the movement of a molecule or ion across the membrane. Other proteins couple the movement of one molecule or ion against its concentration gradient with the movement of another down its gradient, using the energy released by the downhill movement of one molecule or ion to drive the uphill movement of another. Proper functioning of any cell relies on a precise balance between such import and export of various molecules and ions.

We begin our discussion of membrane transport proteins by reviewing some of the general principles of transport across membranes and distinguishing between three major classes of such proteins. In subsequent sections, we describe the structure and operation of specific examples of each class and show how members of families of homologous transport proteins have different properties that enable different cell types to function appropriately. We also explain how specific combinations of transport proteins in both the plasma membrane and organelle membranes enable cells to carry out essential physiological processes, including the maintenance of cytosolic pH, the accumulation of sucrose and salts in plant cell vacuoles, and direction of the flow of water in both plants and animals. The cell’s resting membrane potential is an important consequence of selective ion transport across membranes, and we consider how this potential arises. Epithelial cells, such as those lining the small intestine, use a combination of membrane transport proteins to transport ions, sugars and other small molecules, and water from one side of the cell to the other. We will see how our understanding of this process has led to the development of sports drinks as well as therapies for cholera and other diarrheal diseases.

Note that in this chapter we cover only transport of small molecules and ions; transport of larger molecules, such as proteins and oligosaccharides, is covered in Chapters 13 and 14.