Carbonic anhydrase inhibitors. Inhibition studies of the human secretory isoform VI with anions

The unique secretory isozyme of human carbonic anhydrase (hCA, EC 4.2.1.1), hCA VI, has been cloned, expressed, and . The kinetic parameters for the CO2 hydration reaction proved hCA VI to possess a k(cat) of 3.4 x 10(5) s(-1) and k(cat)/K-M of 4.9 x 10(7) M-1 s(-1) (at pH 7.5 and 20 degrees C). hCA VI has a significant catalytic activity for the physiological reaction, of the same order of magnitude as isoforms CA I or CA IX. A series of anions (such as bicarbonate, chloride, nitrate, etc.) were shown to inhibit the activity of the enzyme, with inhibition constants typically in the range of 0.60-0.90 mM. The best hCA VI inhibitors were cyanide, azide sulfamide, and sulfamate, with inhibition constants in the range of 70-90 mu M. (c) 2006 Elsevier Ltd. All rights reserved.