Cooperative binding

One way to affect the rate of an enzyme catalyzed reaction is to vary the affinity of the enzyme for substrate.


In the situations so far discussed there is a liner relationship between the rate of reaction and the substrate concentration. This linear relationship indicates that the enzyme has the same affinity for the substrate regardless of substrate concentrations.

However, certain enzymes can vary their affinities for substrate. At low substrate concentration, the enzyme will have a lower affinty for substrate than it will at higher substrate concentrations. This means that as the substrate concentration increases the rate of reaction increases disproportionately giving a sigmoidal shaped reaction curve .

A model to explain the sigmoid shape of the curve is called the cooperative binding model. In this model the enzyme has more than one subunit and more than one active site. The term cooperative binding derives from the property that the binding of one molecule of substrate makes it easier for the second molecule of substrate to bind. An excellent example of cooperative binding was discovered by Gehrhardt and Pardee in their study of the enzyme Aspartate transcarbamylase.


At low substrate concentrations

At low substrate concentrations each enzyme molecule encounters only one substrate molecule at a time.The affinity of enzyme for substrate is given by Keq1.

As the substrate binds to the enzyme, the active site occurpied by the substrate changes shape, as does the active site not occupied by enzyme

Because of the change in shape of the enzyme, the unoccupied active site has a different affinity for enzyme: Keq2. In this case K2 is smaller than K1. Thus it is easier for the enzyme to bind to the second active site. However, since the substrate concentration is low, catalysis occurs without any further substrate binding and product is released. When the product is released the active site reverts to its prior shape.Thus the binding of enzyme to substrate is determined by Keq1.

This series of events is animated in a simple manner


High substrate concentrations

At high substrate concentrations the enzyme will encounter another molecule of substrate before product is released and the shape of the active site remains in its modified form.

Thus the rate of the reaction is determined by keq2 and the reaction will occur at a higher rate than that catalyzed solely by Keq1.


Return to modulators of enzyme activity

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One way for a multisubunit enzyme to modulate the rate of reaction is by altering the affinity of the enzyme for substrate.

 

 

Ths can be accomplished is the enzyme