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hydrophobic proteins of molecular weight ~50 kD and are found, principally, in the
endoplasmic reticulum of a variety of cell types. Vertebrate liver is a particularly
rich source; appreciable levels are also found in kidney, testis, and ovary. A soluble
epoxide hydrolase is found in some insects, where it has the role of hydrating epox-
ides of juvenile hormones. The microsomal epoxide hydrolases of vertebrate liver
can degrade a wide range of epoxides, including those of PAHs, PCBs, cyclodiene
epoxides (including dieldrin and analogues thereof), as well as certain endogenous
steroids. Epoxide hydrolase can detoxify potentially mutagenic epoxides formed by
the action of cytochrome P450 on, for example, PAHs. Benzo[
a
]pyrene 4,5 oxide
is an example. Its rapid hydration within the endoplasmic reticulum before it can
migrate elsewhere is important for the protection of the cell. In general, the conver-
sion of epoxides into more polar transdihydrodiols serves a detoxifying function,
although there are a few exceptions to this rule.
2.3.2.5 reductases
A range of reductions of xenobiotics are known to occur both in the endoplasmic
reticulum and cytosol of a number of cell types. However, the enzymes (or other
reductive agencies) responsible are seldom known in particular cases. Some reduc-
tions only occur at very low oxygen levels. Thus, they do not occur under normal
cellular conditions, where there is a plentiful supply of oxygen.
Two important examples of reductive metabolism of xenobiotics are the reductive
dehalogenation of organohalogen compounds, and the reduction of nitroaromatic
compounds. Examples of each are shown in Figure 2.13. Both types of reaction can
take place in hepatic microsomal preparations at low oxygen tensions. Cytochrome
P450 can catalyze both types of reduction. If a substrate is bound to P450 in the
NO
2
NHOH
NH
2
4
e
2
e
1-Nitropyrene
1-Hydroxylaminopyrene
1-Aminopyrene
e
+
Cl
-
CCl
3
CCl
4
Carbon tetrachloride
H
H
H
+
2
e
Cl + Cl
-
Cl
C
Cl
Cl
C
Cl
C
Cl
Cl
C
Cl
Cl
p
,
p
´-DDT
H
p
,
p
´-DDD
fIgure 2.13
Reductase metabolism.
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