Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

36 Chapter 3
3.4 The importance of transition state stabilisation
All catalysts operate by reducing the activation energy of the reaction, by
stabilising the transition state for the reaction. Enzymes do the same, but the
situation is somewhat more complicated since there are usually several transition
states in an enzymatic reaction. We have already seen how an enzyme binds
its substrate reversibly at the enzyme active site. One might imagine that if an
enzyme were to bind its substrate very tightly that this would lead to transition
state stabilisation. This, however, is not the case: in fact, the enzyme does not
want to bind its substrate(s) too tightly!
Shown in Figure 3.8 are free energy curves for a hypothetical enzymecatalysed
reaction proceeding via a single rate determining transition state.
Suppose that we can somehow alter the enzyme, E, so that it binds the
substrate, S, or the transition state, TS, more tightly. In each case the starting
free energy (of E þ S) is the same. In the presence of high substrate concentrations
the enzyme will in practice be fully saturated with substrate, so the
activation energy for the reaction will be governed by the energy diVerence
between the ES complex and the transition state. In Figure 3.8b the enzyme is
able to bind both the substrate and the transition state more tightly (and hence
lower their free energy equally). This, however, leads to no change in the
activation energy, and hence no rate acceleration. In Figure 3.8c the enzyme
(a)
(b) Enzyme binds S and TS more tightly
E + S
ES
E + S
ES
(c) Enzyme binds S more tightly
(d) Enzyme binds TS more tightly
E + S
E + S
ES
ES
Figure 3.8 The importance of transition state stabilisation – a thought experiment.