The roles of carbonic anhydrase in metabolism, cell growth and cancer in animals

Abstract

Viewed from the standpoint of chemical reactivity, CO₂ would appear to be a more appropriate substrate than bicarbonate for carboxylation reactions, since it would be more susceptible to nucleophilic attack. However, in aqueous medium, the equilibrium between dissolved CO₂ and bicarbonate is such that, at physiological pH, bicarbonate is present at some 20-fold higher concentration. Furthermore, bicarbonate probably has greater potential for binding to enzymes since it is a more polar molecule than CO₂. It is perhaps not surprising then, that although the product of decarboxylation reactions in catabolic processes is CO₂, several carboxylating enzymes have evolved to employ bicarbonate, not CO₂, as their substrate. The carboxylating enzymes in animals, which are known to bind bicarbonate as substrate, are the biotin-dependent carboxylases and the carbamoyl phosphate synthetase isozymes. These enzymes bind bicarbonate, but then generally convert it either to CO₂ (biotin-dependent carboxylases) or to an activated form of CO₂ (carbamoyl phosphate synthetases). Carbonic anhydrase (CA) is perhaps alone among enzymes in being able to bind either of these substrates. (For reviews see Rubio, 1986; Knowles, 1989 and O’Leary, 1992).