Info

X 10^5

>1.33 X

104

Adapted from Koshland, D., 1956. Journal of Cellular Comparative Physiology, Supp. 1, 47:217.

Adapted from Koshland, D., 1956. Journal of Cellular Comparative Physiology, Supp. 1, 47:217.

These include the following:

1. Entropy loss in ES formation

2. Destabilization of ES due to strain, desolvation, or electrostatic effects

3. Covalent catalysis

4. General acid or base catalysis

5. Metal ion catalysis

6. Proximity and orientation

Any or all of these mechanisms may contribute to the net rate acceleration of an enzyme-catalyzed reaction relative to the uncatalyzed reaction. A thorough understanding of any enzyme would require that the net acceleration be accounted for in terms of contributions from one or (usually) more of these mechanisms. Each of these will be discussed in detail in this chapter, but first it is important to appreciate how the formation of the enzyme-substrate (ES) complex makes all these mechanisms possible.

Reaction coordinate

FIGURE 16.2 • The intrinsic binding energy of the enzyme-substrate (ES) complex (AGb) is compensated to some extent by entropy loss due to the binding of E and S (TAS) and by destabilization of ES (AGd) by strain, distortion, desolvation, and similar effects. If AGb were not compensated by TAS and AGd, the formation of ES would follow the dashed line.

Reaction coordinate

FIGURE 16.2 • The intrinsic binding energy of the enzyme-substrate (ES) complex (AGb) is compensated to some extent by entropy loss due to the binding of E and S (TAS) and by destabilization of ES (AGd) by strain, distortion, desolvation, and similar effects. If AGb were not compensated by TAS and AGd, the formation of ES would follow the dashed line.

16.3 • The Binding Energy of ES Is Crucial to Catalysis

How is it that X+ is stabilized more than S at the enzyme active site? To understand this, we must dissect and analyze the formation of the enzyme-substrate complex, ES. There are a number of important contributions to the free energy difference between the uncomplexed enzyme and substrate (E + S) and the ES complex (Figure 16.2). The favorable interactions between the substrate and amino acid residues on the enzyme account for the intrinsic binding energy, AGb. The intrinsic binding energy ensures the favorable formation of the ES complex, but, if uncompensated, it makes the activation energy for the enzyme-catalyzed reaction unnecessarily large and wastes some of the catalytic power of the enzyme.

Compare the two cases in Figure 16.3. Because the enzymatic reaction rate is determined by the difference in energies between ES and EX+, the smaller

AG b

E+S

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