What is the function of carbonic anhydrase (CA)?

From the Guidelines

Carbonic anhydrase plays a crucial role in decreasing aqueous production, particularly in the context of glaucoma treatment, as evidenced by its inhibition leading to a 15%–20% reduction in intraocular pressure (IOP) 1.

Key Functions of Carbonic Anhydrase

• Catalyzes the conversion of carbon dioxide and water into carbonic acid, which then dissociates into bicarbonate ions and protons, crucial for maintaining acid-base balance in the body.
• Found in various tissues including red blood cells, kidney tubules, gastric mucosa, and others where pH regulation is vital.
• Facilitates the conversion of bicarbonate back to carbon dioxide for exhalation in the lungs and helps with bicarbonate reabsorption and acid secretion in the kidneys.
• Involved in bone resorption, production of bodily fluids like cerebrospinal fluid and aqueous humor in the eye, and gastric acid secretion.

Clinical Significance

• The use of carbonic anhydrase inhibitors, such as Brinzolamide and Acetazolamide, in treating conditions like glaucoma highlights the enzyme's role in aqueous humor production 1.
• Inhibition of carbonic anhydrase reduces fluid production in the eye, thereby lowering intraocular pressure, a key factor in managing glaucoma.
• Carbonic anhydrase inhibitors are also used in treating altitude sickness and certain types of seizures, further underscoring the enzyme's importance in various physiological processes 1.

From the FDA Drug Label

Acetazolamide is an enzyme inhibitor that acts specifically on carbonic anhydrase, the enzyme that catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid Methazolamide is a potent inhibitor of carbonic anhydrase.

Carbonic anhydrase is an enzyme that catalyzes the reversible reaction involving:

• The hydration of carbon dioxide
• The dehydration of carbonic acid Its inhibition leads to various effects, including:
• Decrease in aqueous humor secretion in the eye
• Decrease in intraocular pressure
• Diuretic effect due to renal loss of HCO3 ion, which carries out sodium, water, and potassium 2
• Alteration in ammonia metabolism and urinary alkalinization 2
• Decrease in urinary citrate excretion and uric acid output 3

From the Research

Carbonic Anhydrase Function

• Carbonic anhydrase (CA) is a zinc-containing enzyme that catalyzes the reversible hydration of carbon dioxide: CO2 + H2O <--> HCO3(-) + H+ 4
• The enzyme plays a crucial role in various physiological processes, including the regulation of pH and the transport of carbon dioxide in the body

Mechanism of Action

• The catalytic mechanism of CA involves an attack of zinc-bound OH- on a CO2 molecule loosely bound in a hydrophobic pocket 4
• The resulting zinc-coordinated HCO3- ion is displaced from the metal ion by H2O, and the rate-limiting step is an intramolecular proton transfer from the zinc-bound water molecule to His-64 4

Isoforms and Distribution

• There are three evolutionarily unrelated CA families, designated alpha, beta, and gamma, with all known CAs from the animal kingdom being of the alpha type 4
• There are seven mammalian CA isozymes (CA I-VII) with different tissue distributions and intracellular locations 4

Inhibition and Applications

• CA inhibitors (CAIs) have pharmacologic applications in the treatment of glaucoma, a disease characterized by elevated intraocular pressure (IOP) 5, 6, 7, 8
• CAIs, such as acetazolamide, methazolamide, and dichlorphenamide, are used to reduce IOP by inhibiting CA isozymes present in ciliary processes of the eye 5, 6, 7