Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

32 Chapter 3
(a)
Free
energy
uncatalysed
reaction
transition states
E act(uncat)
SH + PH +
E act(cat)
S
acid-catalysed
reaction
P
∆G
Reaction co-ordinate
(b)
Free
energy
uncatalysed
reaction
transition state
E act(uncat)
S
ES
enzyme-catalysed
reaction
E.Int
EP
P
E act(cat)
∆G
Reaction co-ordinate
Figure 3.4 Free energy proWles for (a) an acid-catalysed reaction and (b) an enzyme-catalysed
reaction which converts substrate S to product P.
using the active site amino acid side chains. Often enzyme-catalysed reactions
are multi-step sequences involving one or more intermediates, as illustrated in
Figure 3.4. An enzyme–substrate intermediate, ES, is formed upon binding of
the substrate, which is then converted to the enzyme–product complex, EP,
either directly or via one or more further intermediates.
In both catalysed reactions shown in Figure 3.4 the overriding consideration
as far as rate acceleration is concerned is transition state stabilisation. Just as in
non-enzymatic reactions there is acid–base and nucleophilic catalysis taking
place at enzyme active sites. However, the secret to the extraordinary power of
enzyme catalysis lies in the fact that the reaction is taking place as the substrate
is bound to the enzyme active site. So, what was in the non-enzymatic case
an intermolecular reaction has eVectively become an intramolecular reaction.
The rate enhancements obtained from these types of proximity eVects can