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Enzymes are Wonderful Catalysts 47
3.8 Catalytic perfection
How fast is it possible for enzyme-catalysed reactions to proceed Is there a
limit to the rate acceleration achievable by enzymes The answer is yes, and a
small number of enzymes have achieved it. For extremely eYcient enzymes, the
rate of reaction becomes limited by the rate at which a substrate can diVuse
onto its active site and diVuse away into solution – the so-called diVusion limit.
This diVusion limit for collision of enzyme and substrate corresponds to a
bimolecular rate constant of approximately 10 8 m 1 s 1 . We can compare this
value with the bimolecular rate constant for reaction of free enzyme with free
substrate, which is the catalytic eYciency k cat =K M (see Section 4.3).
Many enzymes have catalytic eYciencies of 10 6 to 10 7 m 1 s 1 , but a small
number have k cat =K M values which are at the diVusion limit – these are listed in
Table 3.2. One of these is the enzyme acetylcholinesterase, which is involved in
the propagation of nerve impulses at synaptic junctions: a process for which the
utmost speed is necessary. For these enzymes the rate-determining step has
become the diVusion of substrates onto the active site. As fast as a substrate
diVuses onto the active site it is processed by the enzyme before the next
molecule of substrate appears. These are truly wonderful catalysts.
3.9 The involvement of protein dynamics in enzyme catalysis
Our understanding of such high rates of catalysis in enzymes is still incomplete.
Chemical models for enzyme catalysts, and catalytic antibodies which function
via transition state stabilisation (see Chapter 12), are orders of magnitude less
active catalysts than the above examples. Therefore, there are likely to be other
factors that enzymes use to achieve high rates of catalysis.
Table 3.2 Catalytic eYciencies of some diVusion-limited enzymes.
Enzyme Reaction type k cat =K M (m 1 s 1 )
Superoxide dismutase Redox dismutation 3:0 10 9
Fumarase Hydration 2:0 10 9
Cytochrome c peroxidase Redox peroxidase 6:0 10 8
Triose phosphate isomerase Keto/enol isomerase 3:8 10 8
Acetylcholinesterase Ester hydrolysis 1:4 10 8
Ketosteroid isomerase Keto/enol isomerase 1:3 10 8
b-Lactamase b-lactam hydrolysis 1:0 10 8