NATURE OF ANION INHIBITION OF HUMAN RED-CELL CARBONIC-ANHYDRASES

We studied anionic inhibition of the reaction CO2 + OH-⇄ HCO3- catalyzed by human red cell carbonic anhydrase B (I) and C (II), using iodide and cyanate. In the forward reaction with respect to CO2 as the substrate, inhibition was mixed but favoring noncompetitive; the back reaction, with HCO3- as the substrate, yielded strict competitive kinetics. Mean inhibition constants, KI, in the pH range 7.2-7.5 are: iodide, 0.5 mm for enzyme B and 16 mm for C; cyanate, 0.8 μm for B and 20 μm for C. When OH- was considered as the substrate for the forward reaction, cyanate and chloride behaved as competitive inhibitors. The true inhibition constant (KI0) for cyanate (calculated for infinitely low OH-) is 0.4 μm for enzyme B and 4 μm for C. Apart from the difference in anion affinity and some 10-fold higher activity of C > B, the isozymes showed similar patterns of inhibition. Data agree with generally proposed mechanisms describing the active site as ZnH2O with pKa of about 7. © 1979.