Enzyme Activation by Metal Ions

Earlier we mentioned the fact that certain enzymes exhibit enhanced activity in the presence of specific metal ions. For example, Mg plays a 

The product, A—0P2 0 is adenosine diphosphate, ADP. The transfer of a phosphate group is also assisted by a metal ion in the reaction between glucose and ATP. 

A reaction scheme that illustrates the role of the metal ion in the enzyme activity can be shown by the following reactions, in which E represents the enzyme, S is the substrate, M is the metal ion, P is the product, and EM is the enzyme-metal complex. The rate constant for the formation of the enzyme-metal complex is and that for its dissociation is k-.  

It is possible to analyze this mechanism by means of the stationary state 

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Alkaline phosphatase exists in two forms in animal tissues, one activated by added Mg(II) or Mn(II) and not inhibited by F or CN ions, the other independent of added divalent ions but inhibitable by cyanide . Yeast phosphatase, active at neutral pH, is activated by divalent metal ions in the order Mg > Mn > Ni, Co, Fe ". Metal analysis of purified kidney phosphatase reveals a mixture of bound ions Zn, Cu, Mn, Mg, and Fe . This variety of responses illustrates a classical problem in studies of enzyme activation by metal ions defining the species that is of greatest importance in vivo. 

FIGURE 1.6 In vitro inhibition of enzyme activity by metal ions is correlated with the absolute value of the logarithm of the first hydrolysis constant (i.e., K(,h for M"++ HjO —> MOH"" + H+) and the softness index (Op). Inhibition data for these three enzymes were produced by Christensen (1971/1972) and Christensen and Tncker (1976). White diamonds=catfish carbonic anhydrase ICjq, grey sqnares=white sucker lactic dehydrase ICjo and black triangles = white sucker glutamic oxaloacetic transaminase ICjo-... 

In concluding this chapter, it should be noted that we have presented various models of enzyme mechanisms in which metal ions participate. We have seen that reactions catalyzed by metalloenzymes or enzymes activated by metal ions span a remarkably broad spectrum of reaction types. Of course many facets such as the remarkable speed and specificity of enzyme catalysis have not received complete explanation on the basis of model system chemistry. However, the missing link may be found at the point where biological molecules deviate from the model systems. Here, perhaps the most interesting chemical features will be found (258,259). 

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