Evolutionary links between intra- and extracellular acid-base regulation in fish and other aquatic animals

The acid-base relevant molecules carbon dioxide (CO₂ ), protons (H⁺ ), and bicarbonate (HCO₃^- ) are substrates and end products of some of the most essential physiological functions including aerobic and anaerobic respiration, ATP hydrolysis, photosynthesis, and calcification. The structure and function of many enzymes and other macromolecules are highly sensitive to changes in pH, and thus maintaining acid-base homeostasis in the face of metabolic and environmental disturbances is essential for proper cellular function. On the other hand, CO₂ , H⁺ , and HCO₃^- have regulatory effects on various proteins and processes, both directly through allosteric modulation and indirectly through signal transduction pathways. Life in aquatic environments presents organisms with distinct acid-base challenges that are not found in terrestrial environments. These include a relatively high CO₂ relative to O₂ solubility that prevents internal CO₂ /HCO₃^- accumulation to buffer pH, a lower O₂ content that may favor anaerobic metabolism, and variable environmental CO₂ , pH and O₂ levels that require dynamic adjustments in acid-base homeostatic mechanisms. Additionally, some aquatic animals purposely create acidic or alkaline microenvironments that drive specialized physiological functions. For example, acidifying mechanisms can enhance O₂ delivery by red blood cells, lead to ammonia trapping for excretion or buoyancy purposes, or lead to CO₂ accumulation to promote photosynthesis by endosymbiotic algae. On the other hand, alkalinizing mechanisms can serve to promote calcium carbonate skeletal formation. This nonexhaustive review summarizes some of the distinct acid-base homeostatic mechanisms that have evolved in aquatic organisms to meet the particular challenges of this environment.