Human carbonic anhydrase II (CA II)

Human carbonic anhydrase II is a highly active, monomeric zinc-containing metalloenzyme that catalyzes the rapid, reversible conversion of carbon dioxide (CO₂) and water to bicarbonate (HCO₃⁻) and protons (H⁺). The enzyme is essential for cellular and systemic pH regulation, and its activity is crucial in several physiological processes, including respiration, renal acid-base balance, bone resorption, and maintenance of fluid homeostasis. CA II is characterized structurally by its conserved active site, which contains a zinc ion coordinated by three histidine residues (His94, His96, His119), and a proton shuttle residue (His64), facilitating efficient proton transfer during catalysis. Dysregulation or genetic defects in this enzyme are associated with diseases such as osteopetrosis—due to impaired bone resorption—and renal tubular acidosis, owing to compromised bicarbonate reabsorption. Pharmacologically, CA II is targeted by several drugs, especially inhibitors used in the treatment of glaucoma, epilepsy, and for diuretic purposes, with most inhibitors functioning by blocking the zinc-active site. Potential therapeutic challenges include acidosis and systemic electrolyte imbalance from non-selective inhibition.

Other names

Carbonic anhydrase 2CA2 (gene symbol)HCA IIhCAII

Most drugs are inhibitors that bind the active site, often chelating the zinc ion, thereby preventing CO₂ hydration (e.g., sulfonamide class drugs) Inhibition lowers intraocular pressure (useful for glaucoma), alters acid-base balance (for diuretic action), or modulates neuronal excitability (for epilepsy)