Carbonic anhydrases (CA) are a family of ancient zinc metalloenzymes found in almost all living organisms. All CA can be divided into 3 distinct classes (α, β, and γ) that evolved independently and have no significant homology in sequence and overall folding. All functional CA catalyze the reversible hydration of CO2 into HCO3- and H+ and contain a zinc atom in the active sites essential for catalysis. There are many isoforms of CA in mammals and they all belong to the α class (1,2).
CA2 is a cytosolic member of the α class. It is the most widely distributed isoform among the mammalian CAs (1). Defects in CA2 are associated with osteopetrosis and renal tubular acidosis (3-5). Elevated expression of CA2 is observed in patients with Alzheimer��s disease and the developing brains of Down syndrome patients (6,7). CA2 is also overexpressed in Gastrointestinal Stromal Tumors (GISTs) and is considered a useful marker for diagnosis (8). Recently, CA2 was reported to facilitate transporter activity of the monocarboxylate transporter isoform 1 and 4 (MCT1/4) independent of its own catalytic activity (9,10)
