Figure 3–47 enzymatic acceleration of chemical reactions by decreasing the activation energy. There is a single transition state in this example. However, often both the uncatalyzed reaction (A) and the enzyme-catalyzed reaction (B) go through a series of transition states. In that case, it is the transition state with the highest energy (ST and EST) that determines the activation energy and limits the rate of the reaction. (S = substrate;  P = product of the reaction; ES = enzyme–substrate complex; EP = enzyme– product complex.)
Because this tight binding greatly lowers the energy of the transition state, the enzyme greatly accelerates a particular reaction by lowering the activation energy that is required (Figure 3–47).
Figure 3–48 compares the spontaneous reaction rates and the corresponding enzyme-catalyzed rates for five enzymes. Rate accelerations range from 109 to 1023. Enzymes not only bind tightly to a transition state, they also contain precisely positioned atoms that alter the electron distributions in the atoms that participate directly in the making and breaking of covalent bonds. Peptide bonds, for example, can be hydrolyzed in the absence of an enzyme by exposing a polypeptide to either a strong acid or a strong base. Enzymes are unique, however, in being able to use acid and base catalysis simultaneously, because the rigid framework of the protein constrains the acidic and basic residues and prevents them from combining with each other, as they would do in solution (Figure 3–49).
The fit between an enzyme and its substrate needs to be precise. A small change introduced by genetic engineering in the active site of an enzyme can therefore have a profound effect. Replacing a glutamic acid with an aspartic acid in one enzyme, for example, shifts the position of the catalytic carboxylate ion by only 1 Å (about the radius of a hydrogen atom); yet this is enough to decrease the activity of the enzyme a thousandfold.
To demonstrate how enzymes catalyze chemical reactions, we examine an enzyme that acts as a natural antibiotic in egg white, saliva, tears, and other secretions. Lysozyme catalyzes the cutting of polysaccharide chains in the cell walls of bacteria. The bacterial cell is under pressure from osmotic forces, and cutting even a small number of these chains causes the cell wall to rupture and the cell to burst. A relatively small and stable protein that can be easily isolated in large quantities, lysozyme was the first enzyme to have its structure worked out in atomic detail by x-ray crystallography (in the mid-1960s).
The reaction that lysozyme catalyzes is a hydrolysis: it adds a molecule of water to a single bond between two adjacent sugar groups in the polysaccharide chain, thereby causing the bond to break (see Figure 2–9). The reaction is energetically favorable because the free energy of the severed polysaccharide chain is lower progress of reaction activation energy for catalyzed reaction
Figure 3–48 The rate accelerations caused by five different enzymes.