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Enzymatic Redox Chemistry 145
C
OH
oxygen
N
rebound
C H
Fe III
O N N
N N
Fe IV
N N
C H
concerted
insertion of O
N
O
N
Fe III
N
N
N
C
N
OH
N
Fe III
N
N
Figure 6.31 Mechanisms for oxygen insertion in P 450 mono-oxygenases.
O
P450cam
O
2 H
O 2 , NADPH
OH
1 H
1 H
RETENTION
Figure 6.32 Stereochemistry of P450cam.
The best characterised enzyme of this class is P450cam, which catalyses the
stereospeciWc hydroxylation of camphor. This reaction has been shown by
deuterium labelling to proceed with retention of stereochemistry at the position
of hydroxylation, as shown in Figure 6.32. Retention of stereochemistry is
generally found in other P 450 -dependent hydroxylases. The structure of
P450cam is shown in Figure 6.33.
P 450 -dependent enzymes also catalyse other types of oxidative reactions: one
common example is demethylation. This reaction can be rationalised as shown in
Figure 6.34 by hydroxylation of the terminal methyl group as above, generating a
labilehemi-acetalwhichbreaksdown,liberatingthefreealcoholandformaldehyde.
Other haem-dependent enzymes utilise hydrogen peroxide instead of dioxygen
to access the iron(III)-peroxide intermediate directly – these enzymes are known as
peroxidases. An important function of peroxidases in plants, where they are widely
found, is to initiate lignin formation by abstraction of H . , as will be discussed in
Section 7.10. Finally, the chloroperoxidases are a family of haem-dependent
enzymes found in marine organisms which catalyse the formation of carbon–
chlorine bonds in organic molecules. These enzymes also use hydrogen peroxide
to access the iron(III)-peroxide intermediate, which reacts with a chloride ion to
generate an electrophilic hypochloritespecies (i.e. a ‘Cl þ ’ equivalent). Formation of
a carbon–chlorine bond with a phenol substrate is shown in Figure 6.35.