Zinc and Copper Enzymes

16-3 Zinc is found in more than 80 enzymes. Two of these, carboxypeptidase and carbonic anhydrase, will be discussed here. Copper is also a common metal in enzymes and is present in four different forms. Two of the copper enzymes will also be described. 

FIGURE 16-10 Proposed Mechanism of Carboxypeptidase Action. Transfer of several hydrogen 

In a few cases, theoretical calculations of transition state and intermediate energies and geometries provide confirmation of experimental studies of the mechanism of enzyme reactions and suggest directions for further study. One of these is the hydration of carbon dioxide catalyzed by carbonic anhydrase, a zinc enzyme. Below pH 7, the uncatalyzed reaction HC03 + H2O + CO2 is favored. Above pH 7, the reaction is 

HC03 OH + CO2, catalyzed by carbonic anhydrases I, II, and III. II is particularly active, with a rate enhancement of 10 or more, approaching a diffusion-controlled rate.  

The active site has a zinc(II) ion bonded to three histidine imidazole groups and a fourth site occupied by water or hydroxide ion, L3Zn OH, where L = imidazole N from histidine. Experimentally, the enzyme loses activity below pH 7, indicating that an ionizable group of pK 1 is part of the active site. In addition, it is known that the product of the hydration of CO2 is HCO3 , would be expected in neutral or basic solution. 

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