Carbonic anhydrase is a type of protein known as an enzyme. Enzymes are biological catalysts that increase the speed of chemical reactions within living organisms. Found in various tissues, including red blood cells, the stomach, pancreas, and kidneys, this enzyme is part of a family of proteins that are important for several physiological processes. At least 14 different forms, or isoforms, of carbonic anhydrase have been identified in mammals. These enzymes are metalloenzymes, meaning they contain a zinc ion in their active site.
The Core Chemical Reaction
The primary function of carbonic anhydrase is to accelerate the interconversion of carbon dioxide (CO2) and water (H2O) into carbonic acid (H2CO3). This reaction is reversible, and once formed, carbonic acid can rapidly dissociate into a bicarbonate ion (HCO3−) and a hydrogen ion (H+). The enzyme facilitates this conversion at a high rate—up to a million times faster than the reaction would occur on its own.
The direction of the reaction is dictated by its location in the body and the local concentration of its substrates. In tissues where CO2 is abundant, the enzyme drives the reaction toward producing bicarbonate and hydrogen ions. Conversely, in environments where CO2 levels are low, such as the lungs, it catalyzes the reverse reaction, converting bicarbonate back into CO2 and water. This adaptability allows the enzyme to manage CO2 levels and maintain pH balance.
Physiological Roles in the Body
The activity of carbonic anhydrase is important for respiration, specifically the transport of carbon dioxide from body tissues to the lungs. As cells produce CO2, it diffuses into the bloodstream. Inside red blood cells, carbonic anhydrase quickly converts this CO2 into bicarbonate ions. This conversion allows the blood to carry large amounts of CO2 in the form of bicarbonate, with about 70% of CO2 transported in this manner. When the blood reaches the lungs, the enzyme reverses the process, turning bicarbonate back into CO2, which is then exhaled.
In the kidneys, carbonic anhydrase is involved in regulating the body’s acid-base balance. The enzyme’s function in the renal tubules helps the body manage the reabsorption of bicarbonate and the secretion of acid. This control over bicarbonate ions influences blood pH, keeping it within a stable range.
Beyond respiration and pH balance, carbonic anhydrase has several other localized functions. In the stomach, it participates in the secretion of hydrochloric acid. In the eye, the enzyme’s activity is linked to the production of aqueous humor, the fluid that maintains pressure within the eye. It also helps to make pancreatic juices alkaline and saliva neutral.
Medical Relevance and Inhibitors
The enzyme’s functions make it a target for certain medications. Carbonic anhydrase inhibitors work by blocking the enzyme’s action for a therapeutic effect. These inhibitors are used to treat a variety of medical conditions by altering fluid balance and pH in targeted tissues. Acetazolamide and Methazolamide are examples of carbonic anhydrase inhibitors.
One of the primary uses for these inhibitors is in the treatment of glaucoma. In the eye, carbonic anhydrase contributes to the production of aqueous humor. By inhibiting this enzyme, the rate of fluid production decreases, which in turn lowers the pressure inside the eye. This reduction in intraocular pressure helps manage glaucoma, with decreases of 15% to 20% reported.
These inhibitors are also effective in treating altitude sickness. At high altitudes, the body needs to acclimatize to lower oxygen levels, and carbonic anhydrase inhibitors can assist this process by altering blood pH. The drugs are also used as diuretics to remove excess fluid and to manage certain types of seizures.
Carbonic Anhydrase Deficiency
While medical intervention can intentionally block carbonic anhydrase, rare genetic mutations can cause a natural deficiency of the enzyme. This inherited condition means the body produces a dysfunctional or insufficient amount of a specific carbonic anhydrase isoform.
The most common form, carbonic anhydrase II deficiency syndrome, is characterized by a trio of symptoms: osteopetrosis (abnormally dense bones), renal tubular acidosis (a condition where the kidneys fail to properly acidify urine), and cerebral calcification. The metabolic acidosis results from the kidneys’ inability to reclaim bicarbonate and excrete hydrogen ions effectively. This imbalance disrupts the body’s pH.
Patients with this syndrome often experience developmental delays and intellectual disabilities. The cerebral calcification can lead to neurological symptoms, including seizures. The combination of skeletal, renal, and neurological issues highlights the widespread importance of the enzyme’s function throughout the body.