In some cases the problem of forcing a substrate up its concentration gradient is solved by coupling that upward movement to the downward flow of another substrate. In this way the energy-expending diffusion of the driving substrate powers the energy-absorbing movement of the driven substrate from low concentration to high. Because this type of active transport is not powered directly by the energy released in cell metabolism (see below Primary active transport), it is called secondary.
There are two kinds of secondary active transport: counter-transport, in which the two substrates cross the membrane in opposite directions, and cotransport, in which they cross in the same direction.
An example of this system (also called antiport) begins with the sugar transporter described above. There are equal concentrations of glucose on both sides of the cell. A high concentration of galactose is then added outside the cell. Galactose competes with glucose for binding sites on the transport protein, so that mostly galactose—and a little glucose—enter the cell. The transporter itself, undergoing a conformational change, presents its binding sites for sugar at the inner face of the membrane. Here, at least transiently, glucose is in excess of galactose; it binds to the transporter and leaves the cell as the transporter switches back to its original conformation. Thus, glucose is pumped out of the cell against its gradient in exchange for the galactose riding into the cell down its own gradient.
Many counter-transport systems operate across the cell membranes of the body. A well-studied system (present in red blood cells, nerve cells, and muscle cells) pumps one calcium ion out of the cell in exchange for two or three sodium ions. This system helps maintain the low calcium concentration required for effective cellular activity. A different system, present in kidney cells, counter-transports hydrogen ions and sodium ions in a one-for-one ratio. This is important in stabilizing acidity by transporting hydrogen ions out of the body as needed.
In co-transport (sometimes called symport) two species of substrate, generally an ion and another molecule or ion, must bind simultaneously to the transporter before its conformational change can take place. As the driving substrate is transported down its concentration gradient, it drags with it the driven substrate, which is forced to move up its concentration gradient. The transporter must be able to undergo a conformational change when not bound to either substrate, so as to complete the cycle and return the binding sites to the side from which driving and driven substrates both move.
Sodium ions are usually the driving substrates in the co-transport systems of animal cells, which maintain high concentrations of these ions through primary active transport. The driven substrates include a variety of sugars, amino acids, and other ions. During the absorption of nutrients, for example, sugars and amino acids are removed from the intestine by co-transport with sodium ions. After passing across the glomerular filter in the kidney, these substrates are returned to the body by the same system. Plant and bacterial cells usually use hydrogen ions as the driving substrate; sugars and amino acids are the most common driven substrates. When the bacterium Escherichia coli must metabolize lactose, it co-transports hydrogen ions with lactose (which can reach a concentration 1,000 times higher than that outside the cell).
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