Biotransformation (Metabolism) of Pesticides - Pesticide Biotransformation and Disposition - page 74

The enzymes of plants and microorganisms are responsible for a wide range of bio-
transformations ( Matsumura, 1985 ) and, as a result, an animal feeding on plants may
ingest one or more derivatives produced in or on the plant and thus outside of the
body of the animal, as well as the compound originally applied to the plant. In addi-
tion, some pesticides may be metabolized by bacteria in the intestine, still external to
the cells of the animal itself. An example of this is reduction of parathion to amino-
parathion by rumen bacteria ( Ahmed et al., 1958 ). Although all of these possibilities
should be kept in mind, they are usually of secondary importance. Moreover, many
derivatives known to be formed by light, plants, or microorganisms are also formed by
mammalian enzymes.
A more recent example ( Hainzl and Casida, 1996 ) describes a photochemical reac-
tion of fipronil leading to a neuroactive product, trifluromethylpyrozole.
BIOTRANSFORMATION
The most frequently studied bioconversions of pesticides are those resulting from
metabolism catalyzed by the cytochrome P450 (CYP)-dependent monooxygenases
( Buratti et al., 2005; Ecobichon, 2001; Hodgson and Levi, 2001; Hodgson and Meyer,
1997, 2010; Hodgson et al., 1991; Kulkarni and Hodgson, 1980, 1984a,b; Kulkarni
et al., 1984; Reponen et al., 2010 ). The substantial number of known CYP-catalyzed
reactions with pesticide substrates demonstrates the extensive knowledge base for this
large group of enzymes ( Hodgson, 2003, 2011; Hodgson and Levi, 2001 ). Metabolism
by flavin-containing monooxygenase (FMO) isoforms is also frequently studied and
many FMO substrates are common to both CYPs and FMOs ( Hodgson and Levi,
1992; Tynes and Hodgson, 1985a,b ). Metabolism by other enzymes, including phase
I reactions catalyzed by prostaglandin H synthetase/cyclooxygenase, molybdenum
hydroxylases/aldehyde and xanthine oxidases, alcohol and aldehyde dehydrogenases,
and esterases, is often important for specific pesticides. Phase II conjugations important
for pesticide metabolism include those important for the metabolism of the products
of xenobiotic oxidations, especially those phase II reactions catalyzed by the N -acetyl-,
sulfo-, uridine diphosphate (UDP)-, glucuronyl-, methyl-, and amino acid taurine and
glycine transferases ( Cerrara and Periquet, 1991 ). Glutathione S -transferases (GSTs) are
important catalysts in primary reactions involving nucleophilic substitution of many
chlorinated pesticides as evidenced by the frequent detection of their mercapturates as
human urinary metabolites. Depending upon the substrate, examples of both detoxi-
cation and activation can be found with any of these enzymes, although metabolic
activations by CYP isoforms to form damaging electrophiles reactive with critical
nucleophilic sites of proteins and DNA have been the best characterized activation
reactions ( Table 5.1 ). Human polymorphisms have been found for most, if not all,
of the metabolic enzymes important for pesticide metabolism, and epidemiological