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Carbonic anhydrase 2 (CA2) is a highly efficient zinc-containing metalloenzyme that catalyzes the reversible hydration of carbon dioxide to bicarbonate and a proton (UniProt: P00918). It is expressed ubiquitously but is particularly abundant in erythrocytes, the gastrointestinal tract, and the kidneys, where it plays a fundamental role in pH regulation, CO2 transport, and electrolyte balance (NCBI Gene: 760). In the ciliary body of the eye, CA2 activity is essential for the secretion of aqueous humor; consequently, its inhibition is a primary therapeutic strategy for lowering intraocular pressure in patients with glaucoma (PubMed: 25205493). Pharmacological inhibition of CA2, typically achieved via sulfonamide-based drugs like acetazolamide or dorzolamide, reduces bicarbonate production and subsequent fluid secretion (DrugBank: DB00445). Beyond its role in fluid dynamics, CA2 is involved in bone resorption by osteoclasts, and its genetic deficiency leads to a syndrome of autosomal recessive osteopetrosis, renal tubular acidosis, and cerebral calcification (PubMed: 1558815). CA2 inhibitors are also utilized clinically for the treatment of altitude sickness, edema, and certain forms of epilepsy (StatPearls: NBK541081).
Reversible inhibition of the zinc-containing active site of the enzyme, which prevents the hydration of carbon dioxide into bicarbonate and protons, thereby reducing fluid secretion and altering pH (PubMed: 25205493).
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