The catalatic decomposition of peroxide does involve radical produc- tion on the heme

moiety of the catalase enzyme. Thus the two-electron reduction of peroxide to water involves
oxidation of the resting ferric heme to an oxo-ferryl(FeIV) porphyrin p-cation radical (1), eq. (1)
where one of the oxidizing equivalents is stored on the porphyrin macrocycle.1 However, the
unpaired electron is sufficiently delocalized and sterically protected by the protein that these
porphyrin free radicals are surpris- ingly stable and consequently exhibit few typical radical
reactions.2 The second catalytic step to complete the enzymatic cycle involves the two electron
oxidation of peroxide to dioxygen and the reduction of 1 to the resting ferric state, eq. (2).

The peroxidases, typified by horseradish peroxidase (HRP), show the same initial reaction
with peroxide to generate 1, but now 1 is used to bring about two single one-electron oxidations
of aromatic amines and phenols (eq. 3). The resulting radicals then play important roles in the
secondary metabolism of plants.3

Cytochrome P-450 is nature's most powerful in vivo oxidant as well as being a very
powerful reductant. During the normal enzymatic cycle radicals are generated to achieve the
final substrate oxidations. During this process a variety of radical (or radical-generating) species
may be released into the cell. In order to afford the maximum protection to the heme and the
radicals generated in its vicinity, steric protection is provided by the protein, with the heme
buried deep in the interior. This can be compared to myoglobin, which does not use highly
reactive inter- mediates during its cycling, where the heme is quite exposed (Figure 1).
Cytochromes P-450 are found in all forms of life and they catalyze a diverse series of
oxidations.4 Nevertheless the basic mechanisms by which they function are similar. Scheme 2
shows the catalytic cycle and it is apparent that radicals, or their precursors, may be generated at
each step. Upon binding of substrate (RH) the low-spin resting enzyme (2) is converted into the
more easily reduced high-spin complex (3). A one-electron reduction gives the ferrous

hemeprotein (4), which may have a redox potential as low as -350 mV!6 Interaction of this
powerful re- ductant with halogenated hydrocarbons may follow several paths. For in- stance, a
one-electron reduction of CCl4 gives chloride ion, the resting enzyme and the .CCl3 radical. If
this radical diffuses from the active site it will, of course, initiate lipid peroxidation. Coupling of
an un- paired electron on the ferric heme and the .CCl3 radical generates
Cytochrome P-450 is nature's most powerful in vivo oxidant as well as being a very
powerful reductant. During the normal enzymatic cycle radicals are generated to achieve the
final substrate oxidations. During this process a variety of radical (or radical-generating) species
may be released into the cell. In order to afford the maximum protection to the heme and the
radicals generated in its vicinity, steric protection is provided by the protein, with the heme
buried deep in the interior. This can be compared to myoglobin, which does not use highly
reactive inter- mediates during its cycling, where the heme is quite exposed (Figure 1).
Cytochromes P-450 are found in all forms of life and they catalyze a diverse series of
oxidations.4 Nevertheless the basic mechanisms by which they function are similar. Scheme 2
shows the catalytic cycle and it is apparent that radicals, or their precursors, may be generated at
each step. Upon binding of substrate (RH) the low-spin resting enzyme (2) is converted into the
more easily reduced high-spin complex (3). A one-electron reduction gives the ferrous
hemeprotein (4), which may have a redox potential as low as -350 mV!6 Interaction of this
powerful re- ductant with halogenated hydrocarbons may follow several paths. For in- stance, a
one-electron reduction of CCl4 gives chloride ion, the resting enzyme and the .CCl3 radical. If
this radical diffuses from the active site it will, of course, initiate lipid peroxidation. Coupling of
an un- paired electron on the ferric heme and the .CCl3 radical generates
2