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Journal of Pharmacology And Experimental Therapeutics, Vol. 130, Issue 4, 389-400, 1960
Copyright © 1960 by American Society for Pharmacology and Experimental Therapeutics

A KINETIC ANALYSIS OF CARBONIC ANHYDRASE INHIBITION

Thomas H. Maren 1, Alice L. Parcell 1, and Mohammad N. Malik 1

1 Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida

Eight unsubstituted sulfonamides of widely varying structural type have been studied with respect to their in vitro activity against carbonic anhydrase. Test system was the catalyzed rate of H+ formation from CO2 and water. Two buffer systems, carbonate and barbital, were compared; there were no essential differences in the enzymatic or the inhibition kinetics. The turnover number is of the order of 102 moles CO2/mol E/min.

Both 50% inhibitory concentrations and KI were recorded; in the case of the more active compounds (E) was of the order of (I50), so that KI < (I50).

(E) was estimated from both isolation and kinetic data; in dog erythrocytes it is approximately 26-33 µmol/l. In vitro one enzyme unit is 2.4 x 10-9 M for carbonate buffer, and 1 x l0-9 M for barbital buffer. From these data, the equivalent weight for carbonic anhydrase is 24,500-30,700.

KI ranged from 2.0 x l0-5 M to 1 x 10-9 M. Although these drugs have the same functional group (R-SO2NH2), they differ not only in activity, but in rate of achieving equilibrium, and in one case, extent to which exposure to substrate changes activity.

Data are consistent with inhibition being noncompetitive and reversible.

Note:

After this work was completed, a study appeared by H. Keller et al. (Hoppe-Seyl. Z.316: 172, 1959) with many similar features. In all essential points the two idependent groups agree in both findings and interpretation. S. Lindskog has determined the molecular weight of purified bovine red cell carbonic anhydrase to be 31,000 (Biochim. biophys. Acta 39: 218,1960).

Submitted on March 7, 1960




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