Biotransformation (Metabolism) of Pesticides - Pesticide Biotransformation and Disposition - page 88

Table 5.3 ( Continued)
Phase I isoform Substrate Reference

Diazoxon Mutch et al. (2007); Richter et al. (2009);

Richter and Furlong (1999)

Paraoxon Mutch et al. (2007); Richter et al. (2009);

Richter and Furlong (1999)

( Anand et al., 2006a,b; Crow et al., 2007; Godin et al., 2006, 2007; Huang et al., 2005;
Price et al., 2008; Ross and Crow, 2007; Ross et al., 2006; Wheelock et al., 2005 ) and
humans ( Choi et al., 2002; Crow et al., 2007; Godin et al., 2006, 2007; Huang et al.,
2005; Price et al., 2008; Ross and Crow, 2007; Ross et al., 2006 ), as well as the role
of carboxylases in the human hepatic metabolism of malathion ( Buratti and Testai,
2005 ) (see Tables 5.1 and 5.3 ). The phase I metabolism of methoxychlor, because of its
importance as an environmental endocrine disruptor, has received considerable atten-
tion, particularly in the laboratory of the late David Kupfer (e.g., Bikadi and Hazai,
2008; Hazai et al., 2004; Hu and Kupfer, 2002a,b ).
Other recent studies of hepatic pesticide metabolism include those on azole fungi-
cides ( Barton et al., 2006; Mazur et al., 2007 ), the carbamate insecticide terbutol ( Suzuki
et al., 2001 ), and the herbicide diuron ( Abass et al., 2007a ); see Tables 5.1 and 5.3 .

Phase II Enzymes
Phase II conjugation reactions of pesticides are less well known than phase I, although sev-
eral types of conjugation are known to involve pesticides as substrates ( Dorough, 1984;
Matsumura, 1985; Mehendale and Dorough, 1972; Motoyama and Dauterman, 1980 ).
Glucuronides are important metabolites of carbamates, including banol, carbaryl, and
carbofuran ( Mehendale and Dorough, 1972 ), as well as the endocrine disruptor methoxy-
chlor ( Hazai et al., 2004 ), and some organophosphorus and other pesticides ( Hutson, 1981 ).
Ethereal sulfates, although not important in pesticide metabolism, may be formed from the
oxidative metabolites of carbaryl and carbofuran ( Dorough, 1968, 1970 ). GST is important
in the metabolism of organophosphorus pesticides (Abel et al., 2004a; Choi et al., 2006;
Motoyama and Dauterman, 1980 ) and halogenated herbicides such as the chloroacetanilides
and chloro- S -triazines ( Abel et al., 2004 ; Cho and Kong, 2007 ) as well as thiocarbamate
herbicides such as molinate (Campbell et al. 2008). The conjugation products are typically
further metabolized and, in humans, excreted as urinary mercapturic acids. Interestingly, the
addition of GSH, with a molecular weight of 307, to these 200- to 300-molecular-weight
xenobiotics creates a product that exhibits a species-dependent disposition due to species
differences in size thresholds for biliary excretion compared to renal excretion.
Although not strictly speaking a detoxication reaction, hepatic aliesterase, by form-
ing a stable phosphorylated enzyme with organophosphates (oxons), may serve as an
inert storage protein ( Chambers et al., 1990 ).