Figure 11–5 a model of how a conformational change in a transporter mediates the passive movement of a solute. The transporter is shown in three conformational states: in the outward- open state, the binding sites for solute are exposed on the outside; in the occluded state, the same sites are not accessible from either side; and in the inward-open state, the sites are exposed on the inside. The transitions between the states occur randomly. They are completely reversible and do not depend on whether the solute-binding site is occupied. Therefore, if the solute concentration is higher on the outside of the bilayer, more solute binds to the transporter in the outward-open conformation than in the inward-open conformation, and there is a net transport of solute down its concentration gradient (or, if the solute is an ion, down its electrochemical gradient).
conformational changes that alternately expose the solute-binding site first on one side of the membrane and then on the other—but never on both sides at the same time. The transition occurs through an intermediate state in which the solute is inaccessible, or occluded, from either side of the membrane (Figure 11–5). When the transporter is saturated (that is, when all solute-binding sites are occupied), the rate of transport is maximal. This rate, referred to as Vmax (V for velocity), is characteristic of the specific carrier. Vmax measures the rate at which the carrier can flip between its conformational states. In addition, each transporter has a characteristic affinity for its solute, reflected in the Km of the reaction, which is equal to the concentration of solute when the transport rate is half its maximum value (Figure 11–6). As with enzymes, the binding of solute can be blocked by either competitive inhibitors (which compete for the same binding site and may or may not be transported) or noncompetitive inhibitors (which bind elsewhere and alter the structure of the transporter).
As we discuss shortly, it requires only a relatively minor modification of the model shown in Figure 11–5 to link a transporter to a source of energy in order to pump a solute uphill against its electrochemical gradient. Cells carry out such active transport in three main ways (Figure 11–7): 1. Coupled transporters harness the energy stored in concentration gradients to couple the uphill transport of one solute across the membrane to the downhill transport of another.
2.
ATP-driven pumps couple uphill transport to the hydrolysis of ATP.
3.
Lightor redox-driven pumps, which are known in bacteria, archaea, mitochondria, and chloroplasts, couple uphill transport to an input of energy from light, as with bacteriorhodopsin (discussed in Chapter 10), or from a rate of transport redox reaction, as with cytochrome c oxidase (discussed in Chapter 14).
Amino acid sequence and three-dimensional structure comparisons suggest that, in many cases, there are strong similarities in structure between transporters that mediate active transport and those that mediate passive transport. Some bacterial transporters, for example, that use the energy stored in the H+ gradient across the plasma membrane to drive the active uptake of various sugars are structurally similar to the transporters that mediate passive glucose transport into most animal cells. This suggests an evolutionary relationship between various transporters. Given the importance of small metabolites and sugars as energy sources, it is not surprising that the superfamily of transporters is an ancient one.
We begin our discussion of active membrane transport by considering a class of coupled transporters that are driven by ion concentration gradients. These proteins have a crucial role in the transport of small metabolites across membranes in all cells. We then discuss ATP-driven pumps, including the Na+-K+ pump that is found in the plasma membrane of most animal cells. Examples of the third class of active transport—lightor redox-driven pumps—are discussed in Chapter 14.
Some transporters simply passively mediate the movement of a single solute from one side of the membrane to the other at a rate determined by their Vmax and