Membrane transport and provision of substrates for carbonic anhydrase: in vertebrates

The physiological function of CA in the body can be generalized as facilitation of transport of H+, and/or HCO 3 – across lipid membranes and the aim of this chapter is to explore the need for this facilitation. This function occurs in such diverse processes as the transfer of CO2 produced in tissues, to HCO 3 – in capillary plasma and the reverse in lung capillary blood, the rapid transport of H+ across membranes through which it is relatively impermeable, such as in contracting glycolytic or fast twitch muscle, resorption of Na+ and excretion of H+ in the proximal renal tubule, and the proposed provision of HCO 3 – for synthetic reactions in mitochondria. Maren (1990) has addressed the generalized actions of carbonic anhydrase (CA), but from a slightly different point of view. Widdas et al. (1994) have proposed that the involvement of CA in transport cycles, or systems, is so ubiquitous it should be considered a basic pH dependent function of the enzyme in addition to its catalytic role. Theoretically CA is only needed if the uncatalyzed CO2/HCO 3 – hydration/dehydration reaction rates would be too low and limit transport. To prove this need it is necessary to have quantitative knowledge of the individual flux rates of the three substrates, CO2 which permeates membranes easily, HCO 3 – less easily and H+ with great difficulty, and compare with the uncatalyzed reaction rate. Because the reaction of CO2 and H+ + HCO 3 – is reversible and because there are physiological transport mechanisms which flow in either direction; all three reactants will be termed substrates.