Biology Reference
In-Depth Information
carboxylic acids, preferring aromatic aldehydes and being relatively inactive toward ali-
phatic aldehydes such as acetaldehyde. In the presence of a reducing substrate, aldehyde
oxidase can catalyze reduction reactions such as azo-reduction and nitro-reduction.
Hydrolases and Amidases
Hydrolase and amidase activities (Hodgson, 2008) are known to be important in the
phase I metabolism of xenobiotics, including pesticides. For example, dimethoate is
detoxified by amidase activity and the selective toxicity of malathion is due, in large
part, to the presence in mammals of carboxylesterases not widely distributed in insects.
These enzymes are known from both microsomes and the soluble cytoplasm but are
more commonly found in the latter. It appears likely that, in most cases, amidase and
esterase activities are different activities of the same enzymes with one or the other
activity predominating (
Satoh, 1987
).
DDT Dehydrochlorinase
In the early 1950s, it was demonstrated that DDT-resistant houseflies detoxified DDT
mainly to its noninsecticidal metabolite DDE. The rate of dehydrohalogenation of
DDT to DDE was found to vary between various insect strains as well as between
individuals. The enzyme involved, DDT dehydrochlorinase, also occurs in mammals
but has been studied more intensively in insects.
DDT dehydrochlorinase, a reduced glutathione-dependent enzyme, has been isolated
from the 100,000
g
supernatant of resistant houseflies. Although the enzyme-mediated
reaction requires glutathione, the glutathione concentrations are not altered at the end
of the reaction and it is a matter of controversy as to whether this enzyme is a cytosolic
glutathione transferase.
The lipoprotein enzyme has a molecular mass of 36,000 Da as a monomer and
120,000 Da as the tetramer. The
K
m
for DDT is 5
10
27
M with optimum activ-
ity at pH 7.4. This enzyme catalyzes the degradation of
p,p
-DDT to
p,p
-DDE or the
degradation of
p,p
-DDD (2,2,-bis(
p
-chlorophenyl)-1,1-dichloroethane) to the corre-
sponding DDT ethylene TDEE (2,2-bis(
p
-chlorophenyl)-l-chloroethylene).
o,p
-DDT
is not degraded by DDT dehydrochlorinase, suggesting a
p,p
-orientation requirement
for dehalogenation. In general, the DDT resistance of housefly strains is correlated
with the activity of DDT dehydrochlorinase, although other resistance mechanisms are
known in certain strains.
PHASE II XENOBIOTIC-METABOLIZING ENZYMES
Conjugations may be simple, as in the case of phenol, but often they are more compli-
cated processes in which the final product is derived by several steps. Despite this pos-
sible complexity, it is useful to think of the conjugation of xenobiotics as taking place
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