Membrane-bound carbonic anhydrase (mCA)

Membrane-bound carbonic anhydrases (mCAs) are a specialized group of zinc-metalloproteins that catalyze the rapid interconversion of carbon dioxide and water into bicarbonate and protons at the cell surface. This group includes glycosylphosphatidylinositol (GPI)-anchored isoforms like CA IV and transmembrane isoforms such as CA IX, CA XII, and CA XIV (UniProt: P22748, Q16790, O43570). These enzymes are essential for maintaining pH homeostasis, facilitating CO2 excretion, and supporting ion transport in various tissues, including the kidneys, eyes, and brain (StatPearls: NBK541032). In oncology, CA IX and CA XII are of particular interest as they are strongly upregulated by hypoxia-inducible factor 1-alpha (HIF-1α) in solid tumors. In these settings, they contribute to an acidic tumor microenvironment that promotes chemoresistance, invasion, and metastasis (PubMed: 24512110). Therapeutic strategies targeting these enzymes include small-molecule sulfonamide inhibitors like SLC-0111 and monoclonal antibodies such as Girentuximab (ClinicalTrials.gov: NCT02215850). These agents are being evaluated for their ability to disrupt tumor pH regulation and enhance the efficacy of other treatments. While effective, targeting mCAs requires selectivity to avoid systemic side effects like metabolic acidosis or electrolyte imbalances caused by the inhibition of ubiquitous cytosolic isoforms (PubMed: 30114337). Beyond cancer, inhibitors of membrane-bound CAs like dorzolamide are widely used to reduce intraocular pressure in glaucoma patients (PubMed: 10405310).

Other names

Carbonate dehydrataseMembrane-associated carbonic anhydraseGPI-anchored carbonic anhydraseTransmembrane carbonic anhydraseCarbonic anhydrase IVCarbonic anhydrase IXCarbonic anhydrase XIICarbonic anhydrase XIV

Inhibition of the zinc-catalyzed reversible hydration of carbon dioxide to bicarbonate and protons, thereby modulating intra- and extracellular pH and ion transport.