Carbonic Anhydrase and the Evolution of Cellular CO2 Transport

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9304844 Henry The enzyme carbonic anhydrase (CA), which catalyses the reversible hydration/dehydration of CO2 has been known for many years to function in the systemic transport and excretion of CO2. Recent work, however, has shown that the limiting step in CO2 transport occurs at the cellular level (i.e., diffusion across individual membranes). CA, localized on the "upstream" side of the membrane, facilitates CO2 transport via the catalyzed dehydration of HCO3-, maintaining a high PCO2 in the boundary layer and thus driving CO2 diffusion across the membrane. Therefore, Ca within metabolically active tissue (i.e., muscle) is important for the initial step of CO2 transport form the intracellular compartment to the blood. While this process has been studied in mammalian systems, there is a complete void of information for evolutionarily more primitive organisms. This is a major gap in our understanding of both the evolution of CO2 transport and the evolution of CA function, because metabolically active, contractile tissue (muscle) evolved long before the development of complex respiratory systems. It is quite plausible, therefore, for Ca to have had its evolutionary origins in metabolically active tissue for the purpose of cellular CO2 elimination. This hypothesis will be tested in a number of invertebrate species using a combination of biochemical, physiological, pharmacological, and histochemical techniques. If widespread support for this idea is found among the invertebrates, it will form the basis for a potentially unifying hypothesis for the origin of cellular CA function and the near universal distribution of the enzyme in metabolically active tissues. These experiments will also form the database upon which future experiments on even more primitive organisms will be designed and performed. ***