CA VI

Carbonic anhydrase VI (CA VI) is a zinc-dependent enzyme that catalyzes the reversible hydration of carbon dioxide and is the only secreted isoform within the human α-carbonic anhydrase family^[1][2]. CA VI is produced primarily by serous acinar cells of the salivary and mammary glands and is secreted into saliva and milk, where it contributes to extracellular acid-base regulation and surface homeostasis^[1]. Mechanistically, CA VI participates in pH regulation by accelerating the conversion of carbon dioxide and bicarbonate, thereby supporting buffering processes on oral and upper alimentary tract surfaces^[1][3]. This activity is closely linked to maintenance of the enamel pellicle and protection against excessive acid exposure in the oral cavity and gastrointestinal mucosa^[1][4]. Disease-associated studies have reported that reduced salivary CA VI levels are associated with increased prevalence of dental caries and acid-related epithelial disorders, supporting its relevance as a biomarker and functional component of mucosal defense^[1][4]. Compared with other carbonic anhydrase isoforms, CA VI is distinguished by its extracellular secretion and unique C-terminal structural features, whereas most related α-carbonic anhydrases function as intracellular, membrane-associated, or mitochondrial enzymes^[2]. Structural characterization further demonstrated that human CA VI forms oligomeric assemblies and remains susceptible to inhibition by the classical carbonic anhydrase inhibitor acetazolamide, making it a useful experimental model for investigating extracellular carbonic anhydrase biology and inhibitor interactions^[2][5].