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Carbonic Anhydrase

Carbonic anhydrases are enzymes that catalyze the hydration of carbon dioxide and the dehydration of bicarbonate:

CO2 + H2O <-----> HCO3- + H+

These carbonic anhydrase-driven reactions are of great importance in a number of tissues. Examples include:

Carbonic anhydrase isozymes are metalloenzymes consisting of a single polypeptide chain (Mr ~ 29,000) complexed to an atom of zinc. They are incredibly active catalysts, with a turnover rate (kcat) of about 106 reactions per second! Catalytic activity depends on ionization of a group of pKa 7 and, as you might expect from thinking about when and where the above reactions take place, the hydration reaction depends on the ionized group being in the basic form, and for dehydration in the acidic form.

Carbonic anhydrase inhibitors have been used theraputically. The prototype of such drugs is acetazolamide, which is still sometimes used as a diuretic to treat certain edematous conditions and for therapy of some types of glaucoma. The discovery of this drug is actually an interesting story. It is a member of the sulfonamides, a group of antibacterial agents which, when intially investigated, were shown to induce a metabolic acidosis because they inhibited excretion of hydrogen ion from the kidney.

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