Carbonic anhydrase, CO2 transport and GABA homeostasis: an in-vitro model

In the present work data are reported on the effect played by CO2 transport, operated by carbonic anhydrase (CA), on the decarboxylation of l-glutamic acid (GA), operated by glutamic acid decarboxylase (GAD), to give γ-aminobutyric acid (GABA). It is shown that in a physico-chemical model system in which the rate of GA decarboxylation is continuously monitored by a selective GA biosensor, such a reaction is sharply affected by CA in the presence of an excess of CO2. Further experimental results, obtained in the presence of specific CA and GAD inhibitors (acetazolamide and valproic acid respectively), have shown that the synergic effect between the two enzyme-catalyzed reactions is extremely selective. In this light, it also seems necessary to reconsider the mechanism of action of the CA inhibitor, acetazolamide, used in the past in the treatment of several diseases of the central nervous system.