Carbonic anhydrase (human isoforms) (CA)

Carbonic anhydrases (CAs) are a large family of zinc-containing metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate and a proton (Supuran, C. T., 2008, Nature Reviews Drug Discovery). In humans, there are 15 known isoforms, 12 of which are catalytically active, and they vary significantly in their subcellular localization and tissue distribution (UniProt, 2024). These enzymes are essential for maintaining pH homeostasis, facilitating CO2 transport in red blood cells, and regulating electrolyte secretion in the eyes, kidneys, and gastrointestinal tract (StatPearls, 2023). Due to their widespread physiological roles, CAs are implicated in various diseases, including glaucoma, where CA II and CA IV are targeted to reduce intraocular pressure, and cancer, where CA IX and CA XII are markers of hypoxia and tumor progression (Imtaiyaz Hassan, M., et al., 2013). Most clinical drugs targeting CAs are sulfonamides or sulfamates that bind directly to the zinc ion in the active site to inhibit catalysis (PubChem, 2024). A significant challenge in the field is the development of isoform-specific inhibitors to minimize side effects resulting from the unintended inhibition of "other" CA isoforms across different tissues (Neri, D., & Supuran, C. T., 2011).

Other names

Carbonate dehydratasehCACarbonic anhydrase familyCarbonic dehydratase

Carbonic anhydrase inhibitors (CAIs) typically function by coordinating to the catalytic zinc ion (Zn2+) located at the enzyme's active site, which displaces the zinc-bound water molecule or hydroxide ion and prevents the reversible hydration of carbon dioxide into bicarbonate and protons (Supuran, C. T., 2016, Bioorganic & Medicinal Chemistry).