Mitochondrial carbonic anhydrases VA and VB: Metabolic roles and clinical significance.

Mitochondrial carbonic anhydrases VA and VB (CA VA and CA VB) are localized within the mitochondrial matrix. These zinc-containing enzymes catalyze the reversible hydration of carbon dioxide to bicarbonate and protons, thereby providing bicarbonate for essential mitochondrial metabolic reactions and contributing to intracellular pH balance. CA VA is predominantly expressed in the liver and plays a key role in supplying bicarbonate for pathways such as gluconeogenesis, ureagenesis, and lipogenesis. In contrast, CA VB shows a broader tissue distribution and supports mitochondrial metabolism across multiple organs, although its physiological role is less clearly defined. Mitochondrial CAs are directly linked to metabolic processes required for energy homeostasis. Deficiency of CA VA is associated with metabolic disorders, particularly those involving impaired ammonia detoxification and disruption of intermediary metabolism. This chapter summarizes current knowledge on CA VA and CA VB, including their molecular and structural features, biochemical properties, tissue distribution, and roles in mitochondrial metabolism. In addition, evidence from experimental models, clinical findings related to CA5A mutations, and emerging therapeutic perspectives are discussed.