How does conformational changes in a transporter mediate the passive transport of a solute such as glucose?
A.
An important example of a transporter that mediates passive transport is the glucose transporter in the plasma membrane of many mammalian cell types. The protein, which consists of a polypeptide chain that crosses the membrane at least 12 times, can adopt several conformations—and it switches reversibly and randomly between them. In one conformation, the transporter exposes binding sites for glucose to the exterior of the cell; in another, it exposes the sites to the cell interior.
B.
Because glucose is uncharged, the electrical component of its electrochemical gradient is zero. Thus the direction in which it is transported is determined by its concentration gradient alone. When glucose is plentiful outside cells, as it is after a meal, the sugar binds to the transporter’s externally displayed binding sites; if the protein then switches conformation—spontaneously and at random—it will carry the bound sugar inward and release it into the cytosol, where the glucose concentration is low.
C.
Conversely, when blood glucose levels are low—as they are when you are hungry—the hormone glucagon stimulates liver cells to produce large amounts of glucose by the breakdown of glycogen. As a result, the glucose concentration is higher inside liver cells than outside. This glucose can bind to the internally displayed binding sites on the transporter. When the protein then switches conformation in the opposite direction—again spontaneously and randomly—the glucose will be transported out of the cells and made available for import by other, energy-requiring cells.
D.
The net flow of glucose can thus go either way, according to the direction of the glucose concentration gradient across the plasma membrane: inward if more glucose is binding to the transporter’s externally displayed sites, and outward if the opposite is true. Although passive transporters themselves play no part in controlling the direction of solute transport, they are highly selective in terms of which solutes they will move. For example, the binding sites in the glucose transporter bind only D-glucose and not its mirror image L-glucose, which the cell cannot use as an energy source.