Carbonic anhydrase is a protein that helps regulate the acid-base balance and pH in blood and other animal tissues. It is primarily known for its role in transforming carbon dioxide to bicarbonate to be transported to the lungs. This protein is present in most organisms, from bacteria to plants. It is also of pharmaceutical interest, with several drugs being inhibitors of its activity.
Carbon dioxide (CO2) is produced from aerobic respiration and the breakdown of fats. It is removed from the body by exhalation from the lungs. The carbon dioxide produced throughout the body needs to be transported through the blood to get to the lungs. It is transported in several forms, primarily as bicarbonate, HCO3-. Bicarbonate is CO2- with an OH group attached. When the bicarbonate reaches the lungs, it is transformed back to carbon dioxide, so it can be exhaled from the body.
Carbonic anhydrase converts carbon dioxide to bicarbonate in a reversible reaction, primarily in red blood cells. This reaction can happen spontaneously, but the rate is much too slow for the body’s needs. Being an enzyme, carbonic anhydrase speeds up the reaction rate dramatically. It is one of the fastest enzymes known. This reaction traps the bicarbonate in the cells, since it cannot diffuse in and out of cells like carbon dioxide can.
Carbonic anhydrase has a molecule of zinc at its active site, and is part of a class of enzymes known as metalloenzymes. This is part of the reason humans require zinc in their diet. The carbonic anhydrase mechanism involves a molecule of water binding to the zinc atom. An OH group then binds to the carbon atom of CO2, resulting in a bicarbonate ion. This is followed by the release of H+, a proton.
There are a number of different carbonic anhydrases that are found in different organisms. There are five known classes that appear to have evolved independently. One of the classes is the alpha class that comprises at least 14 forms of human enzymes. Their properties vary depending on the cellular compartment or tissue they are located in.
Many of the forms are extracellular or membrane-bound. This may help to improve the diffusion of carbon dioxide and protons within the cell. Carbonic anhydrase can disrupt intracellular pH gradients by increasing proton movement. This can help the cell to keep a constant cellular pH. Excess intracellular protons can interfere with many cellular reactions.
The role of carbonic anhydrase varies in different tissue. In the stomach, it is involved in the secretion of stomach acid, while it keeps saliva neutral. It also influences the water content of cells in the eyes and kidneys. If the carbonic anhydrases at these locations are absent or not functioning properly, this can lead to disease. For instance, if too much fluid builds up in the eye, it can lead to glaucoma.
Several carbonic anhydrase inhibitors are used commercially as pharmaceutical drugs, primarily to control glaucoma. The most common inhibitor used is acetazolamide. It is also used to treat epilepsy and altitude sickness, along with several other conditions.
In plants, carbon dioxide from the air is converted to sugar in the presence of sunlight by the process of photosynthesis. Excess carbon dioxide is stored in the plant as bicarbonate. Plants use carbonic anhydrase to convert the bicarbonate back to carbon dioxide, so it can be used in photosynthesis.
