Some other types of important membrane transport proteins are also built from inverted repeats. Examples even include channel proteins such as the aquaporin water channel (discussed later) and the Sec61 channel through which nascent polypeptides move into the endoplasmic reticulum (discussed in Chapter 12). It is thought that these channels evolved from coupled transporters, in which the gating functions were lost, allowing them to open toward both sides of the membrane simultaneously to provide a continuous path across the membrane.
In bacteria, yeasts, and plants, as well as in many membrane-enclosed organelles of animal cells, most ion-driven active transport systems depend on H+ rather than Na+ gradients, reflecting the predominance of H+ pumps in these membranes. An electrochemical H+ gradient across the bacterial plasma membrane, for example, drives the inward active transport of many sugars and amino acids.
Transporters in the Plasma Membrane Regulate Cytosolic pH
Most proteins operate optimally at a particular pH. Lysosomal enzymes, for example, function best at the low pH (~5) found in lysosomes, whereas cytosolic enzymes function best at the close-to-neutral pH (~7.2) found in the cytosol. It is therefore crucial that cells control the pH of their intracellular compartments.
Most cells have one or more types of Na+-driven antiporters in their plasma membrane that help to maintain the cytosolic pH at about 7.2. These transporters use the energy stored in the Na+ gradient to pump out excess H+, which either leaks in or is produced in the cell by acid-forming reactions. Two mechanisms are used: either H+ is directly transported out of the cell or HCO3 is brought into the cell to neutralize H+ in the cytosol (according to the reaction HCO3– + H+ →H2O + CO2). One of the antiporters that uses the first mechanism is a Na+–H+ exchanger, which couples an influx of Na+ to an efflux of H+. Another, which uses a combination of the two mechanisms, is a Na+-driven Cl––HCO3 – exchanger that couples an influx of Na+ and HCO3 to an efflux of Cl– and H+ (so that NaHCO3 comes – in and HCl goes out). The Na+-driven Cl––HCO3 exchanger is twice as effective as the Na+–H+ exchanger: it pumps out one H+ and neutralizes another for each Na+ that enters the cell. If HCO3– is available, as is usually the case, this antiporter is the most important transporter regulating the cytosolic pH. The pH inside the cell regulates both exchangers; when the pH in the cytosol falls, both exchangers increase their activity.
A Na+-independent Cl––HCO3 exchanger adjusts the cytosolic pH in the reverse direction. Like the Na+-dependent transporters, pH regulates the Na+-in– dependent Cl––HCO3 exchanger, but the exchanger’s activity increases as the – cytosol becomes too alkaline. The movement of HCO3 in this case is normally out of the cell, down its electrochemical gradient, which decreases the pH of the