Carbonic anhydrase II (CA II) and Carbonic anhydrase III (CA III) (CA II/CA III)

Carbonic anhydrase II (CA II) and Carbonic anhydrase III (CA III) are distinct isoforms of the alpha-carbonic anhydrase family, a group of zinc-containing metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate and a proton [3, 6]. CA II is a ubiquitous and highly active cytosolic enzyme essential for maintaining acid-base homeostasis, regulating intracellular pH, and facilitating fluid secretion in tissues such as the eye, kidney, and brain [8, 12]. It is a well-validated therapeutic target for glaucoma, where its inhibition reduces aqueous humor production, and for epilepsy and edema [12, 14]. In contrast, CA III is primarily expressed in skeletal muscle and possesses much lower CO2 hydratase activity than CA II; however, it plays a specialized role in protecting cells against oxidative stress through its protein-thiolation activity [9, 15]. While CA II is highly sensitive to sulfonamide inhibitors like acetazolamide and dorzolamide, CA III is relatively resistant due to steric hindrance in its active site caused by a bulky phenylalanine residue [9, 16]. Drugs targeting these enzymes primarily function by coordinating with the catalytic zinc ion to block the hydration reaction, thereby altering ion transport and pH-dependent processes [6, 14].

Other names

CA2CA3Carbonate dehydratase IICarbonate dehydratase IIICA-IICA-IIICytosolic carbonic anhydrase IIMuscle-specific carbonic anhydrase III

Inhibition of the zinc-catalyzed reversible hydration of carbon dioxide to bicarbonate and protons, which regulates pH and fluid secretion in various tissues [3, 6, 12].