Carbonic anhydrase 5A, mitochondrial (CA-VA) (CA-VA)

Carbonic anhydrase 5A, mitochondrial (CA-VA) is a zinc-containing metalloenzyme localized within the mitochondrial matrix, primarily in the liver [1, 6, 7]. It plays a fundamental role in intermediary metabolism by catalyzing the reversible hydration of carbon dioxide to bicarbonate [1, 11, 14]. This bicarbonate serves as an essential substrate for four key mitochondrial carboxylases: carbamoyl phosphate synthetase 1, pyruvate carboxylase, propionyl-CoA carboxylase, and 3-methylcrotonyl-CoA carboxylase [1, 11, 18]. Through these interactions, CA-VA is vital for ammonia detoxification via the urea cycle, as well as for gluconeogenesis and de novo lipogenesis [1, 3, 17]. Genetic mutations in the CA5A gene result in CA-VA deficiency, a condition characterized by hyperammonemia and metabolic acidosis in neonates and young children [1, 11, 17]. Beyond its role in rare genetic disorders, CA-VA is a recognized therapeutic target for obesity and type 2 diabetes due to its involvement in fatty acid synthesis [4, 5, 12]. Pharmacological inhibitors such as acetazolamide, topiramate, and zonisamide target CA-VA, although they often exhibit broad activity across multiple carbonic anhydrase isoforms [4, 9, 20]. Therapeutic modulation of CA-VA activity aims to manage metabolic syndromes, though it requires careful monitoring of acid-base balance and electrolyte levels [9, 11].

Other names

CA5ACA-VACAVCAVACarbonate dehydratase VACarbonic anhydrase VCarbonic anhydrase VACarbonic anhydrase 5A

Inhibition of carbonic anhydrase activity by binding to the zinc ion in the active site, preventing the hydration of carbon dioxide to bicarbonate.