2.4 The role of ATP in enzyme-catalyzed reactions

The most common exergonic reaction that is utilized by enzymes to drive endergonic ones is the hydrolysis of the phosphodiester bonds in ATP. While this is a general principle in enzymology, it is important to understand that there is no equally general chemical mechanism of ATP utilization; each enzyme needs to find its own way of actually linking the two reactions. As an example, here is how glutamine synthetase does it. This enzyme uses ATP to produce glutamine from glutamate and ammonia (Figure 2.4-1).

While the net turnover of ATP is hydrolysis, the phosphate group is actually first transferred to the substrate to create an intermediate product, glutamate-5-phosphate. The phosphate group in this compound (a mixed anhydride) is a very good leaving group, which facilitates the subsequent substitution by ammonia. Therefore, the utilization of ATP is an integral part of the reaction mechanism of this enzyme.

We will see additional examples of ATP usage in enzyme catalysis in the remainder of this course.