102
Cytochrome P450
Monooxygenase
Enzyme that reduces O
2
: one oxygen atom is used in substrate modifcation (oFten
hydroxylation), while the other is used to Form water.
Superfamily
A group oF proteins that are evolutionarily related as determined by their primary amino
acid sequence.
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In the original issues oF this Encyclopedia in 1996, there was the article (Volume 1)
on cytochrome P450 monooxygenases. This new article Follows the same Format as
that used previously. However, a great deal oF interesting inFormation on P450s has
appeared in the last six to seven years. Accordingly, it is the goal oF the authors to
present the basic principles oF the P450 system as outlined in the previous article,
while at the same time taking advantage oF new discoveries to provide more depth
in understanding these Fascinating enzymes.
Cytochrome
P450
is
the
generic
name
applied
to
a
large
superFamily
oF hemoprotein, mixed-Function oxidases (monooxygenases) that metabolize a
structurally diverse group oF exogenous and endogenous organic substrates. The
name is derived From the prominent absorption band observed at 450 nm Following
reduction oF the heme iron and its coordination with carbon monoxide. These
enzymes are widely distributed among all biological kingdoms and they catalyze a
reaction oF the general nature
P450
O
2
+
NAD(P)H
Biological reducing equivalents
+
AH
Organic substrate
−−−→
AOH
Hydroxylated organic product
+
H
2
O
+
NAD
(
P
)
+
In the case oF exogenous substrates, this reaction is most Frequently involved in an
organism’s eFFort to detoxiFy Foreign compounds (xenobiotics) From the environment.
In the case oF endogenous substrates, the reaction is generally involved in the
production oF biologically more active compounds (viz. steroid hormones) From less
active compounds (viz. cholesterol).
1
Characteristics of P450s
In 1962, Ryo Sato and Tsuneo Omura
characterized an unusual pigment in a
subcellular Fraction oF rabbit liver, the
endoplasmic reticulum, which showed
an intense absorbance band at 450 nm
upon reduction and coordination with
carbon monoxide. They tentatively named
the
material
‘‘pigment
450 nm’’
or
‘‘cytochrome
P450.’’
The
latter
name
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