Carboanhydrase

Carboanhydrase, more commonly called carbonic anhydrase (CA), is a family of metalloenzymes that catalyze the rapid interconversion of carbon dioxide and water with bicarbonate and protons: CO2 + H2O ⇌ HCO3− + H+. This reaction enables efficient CO2 transport in tissues and blood and supports acid–base balance in organs such as the kidney, lungs, brain, and secretory tissues.

All known vertebrate carbonic anhydrases belong to the alpha class. The active site houses a zinc ion coordinated by three histidine residues; a water molecule bound to zinc acts as the catalytic nucleophile. The enzyme dramatically accelerates the hydration and dehydration steps, allowing rapid adjustment of pH and bicarbonate levels. Inhibitors that coordinate to the zinc ion, such as sulfonamides, block catalysis and are used pharmacologically.

In humans, multiple CA isozymes are encoded and distributed across tissues, providing specialized functions. Cytosolic isozymes include CA I, CA II, and CA III; membrane-associated isozymes include CA IV, CA IX, and CA XII; secreted CA VI is found in saliva and milk. Some isozymes, such as CA IX and CA XII, are associated with pathological states, including cancer, where they can be upregulated and serve as markers or therapeutic targets.

Physiological roles of carbonic anhydrases include facilitating CO2 removal during respiration, supporting renal reabsorption and secretion of bicarbonate, regulating cerebrospinal fluid and gastric pH, and maintaining ocular aqueous humor production. Clinically, carbonic anhydrase inhibitors (for example, acetazolamide and dorzolamide) are used to reduce intraocular pressure in glaucoma and to manage certain forms of edema or altitude sickness.