The anaerobic metabolism of glucose yields lactic acid, and aerobic metabolism yields CO₂, which combines with water to form carbonic acid (H₂CO₃). These weak acids dissociate, yielding H⁺ ions (protons); if these excess protons were not removed from cells, the cytosolic pH would drop precipitously, endangering cellular functions. Two types of cotransporters help remove some of the excess protons generated during metabolism in animal cells. One is a Na⁺HCO₃⁻/Cl⁻ antiporter, which imports one Na⁺ ion, together with one HCO₃⁻, in exchange for export of one Cl⁻ ion. The cytosolic enzyme carbonic anhydrase catalyzes the dissociation of the imported HCO₃⁻ ion into CO₂ and an OH⁻ (hydroxyl) ion:

The OH⁻ ions combine with intracellular protons, forming water, and the CO₂ diffuses out of the cell. Thus the overall action of this transporter is to consume cytosolic H⁺ ions, thereby raising the cytosolic pH. Also important in raising cytosolic pH is a Na⁺/H⁺ antiporter, which couples the movement of one Na⁺ ion into the cell down its concentration gradient to the export of one H⁺ ion.

Under certain circumstances, the cytosolic pH can rise beyond the normal range of 7.2–7.5. To cope with the excess OH⁻ ions associated with elevated pH, many animal cells use an anion antiporter that catalyzes a one-for-one exchange of HCO₃⁻ for Cl⁻ across the plasma membrane. At high pH, this Cl⁻/HCO₃⁻ antiporter exports one molecule of HCO₃⁻ (which can be viewed as a “complex” of OH⁻ and CO₂) in exchange for the import of one molecule of Cl⁻, thus lowering the cytosolic pH. The movement of Cl⁻ down its concentration gradient (Cl⁻_exterior > Cl⁻_cytosol; see Table 11-2) powers the export of HCO₃⁻.

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The activity of all three of these antiporters is regulated by the cytosolic pH, providing cells with a finely tuned mechanism for controlling cytosolic pH. The two antiporters that operate to increase cytosolic pH are activated when the pH of the cytosol falls. Similarly, a rise in pH above 7.2 stimulates the Cl⁻/HCO₃⁻ antiporter, leading to a more rapid export of HCO₃⁻ and a drop in the cytosolic pH. In this manner, the cytosolic pH of growing cells is maintained very close to pH 7.4.