{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Carbonic anhydrase VI (CA6), also known as gustin, is a secreted, zinc‐dependent enzyme that catalyzes the reversible hydration of carbon dioxide. It is predominantly expressed in salivary and mammary glands, where its activity is critical for pH regulation in secretions. CA6 plays a pivotal role in oral physiology by acting as a trophic factor for taste bud development and maintenance. Genetic polymorphisms in the CA6 gene have been linked to variations in taste sensitivity—for example, differences in response to bitter compounds such as 6‐n‐propylthiouracil (PROP) and to salt—through effects on fungiform papilla density and function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": " Moreover, CA6 polymorphisms are associated with dental caries susceptibility—possibly through modulation of the oral microbiota (e.g., influencing Streptococcus mutans colonization) and altering salivary buffering capacity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In the mammary gland, CA6 is involved indirectly in secretory processes by working in concert with zinc transporters that supply Zn necessary for the metallation of key proteins."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Detailed biochemical studies have defined its catalytic efficiency and activation profile by various amino acids and amines."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Although CA6 is best known for its roles in taste perception and oral health, emerging evidence suggests its functions may extend to other tissues. In endothelial cells, for example, local pH regulation is a critical factor in modulating leptin receptor–mediated signaling, implying that CA6 could indirectly influence vascular functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Similarly, while the review of tumor metabolic plasticity focuses on lactate-driven pathways"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", the underlying importance of pH homeostasis in the tumor microenvironment highlights a broader role for carbonic anhydrases. In this regard, CA6 exemplifies the diverse functions of the CA family in maintaining extracellular acidity and influencing cellular metabolism."}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore CA6 as a multifunctional enzyme that is essential not only for taste bud development and the regulation of oral pH (thereby impacting food preferences and dental health) but also as a potential modulator of pH‐dependent processes in vascular and metabolic contexts.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alessandra Padiglia, Andrea Zonza, Elena Atzori, et al. 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