Degradation of Pesticides by Animals
13
species the endogenous substrates are commonly glucuronic acid, sulfate, and
amino acids. Glucose instead of glucuronic acid, is the most common endogenous
substrate in insects and plants (Parke, 1968).
Pesticides usually require some type of phase I metabolism to produce an
-OH, -COOH, -NH2' -NHOH, or -SH site for subsequent conjugation with an
endogenous compound (Smith, 1968; Jenner and Testa, 1978). If the endogenous
compound is glucose, the conjugate is called a glucoside, and when it is glucuronic acid, it is referred to as a glucuronide. The terms that differentiate
between the exogenous and endogenous moieties of the sugar conjugate or glycoside are glycone (sugar moiety) and aglycone (exogenous portion). The other
types of conjugates do not have comparable terms to distinguish between the
exogenous and endogenous portions of any conjugate, so the term exocon has
been used to indicate the exogenous portion, and endocon to note the endogenous
moiety (Dorough, 1976).
1.3. 1. Glycoside Formation
While glucoside conjugation of xenobiotics is rare in mammals, some exceptions are reported in the literature. An example of this is the conjugation of
a xanthine oxidase inhibitor with glucose in dogs, rats, and monkeys (Duggan
et al., 1974). Conclusive evidence that pesticides undergo glucose conjugation
in mammals has yet to be presented.
In vertebrate species, many pesticides or their metabolites are conjugated
as glucuronides. Glucuronic acid does not react directly, but is present in an
active form (uridine diphosphate glucuronic acid, UDPGA), which is synthesized
enzymatically from a-glucose-6-phosphate and glucuronic acid. Conjugation
with a pesticide or its metabolite is mediated by glucuronyltransferase enzymes.
This type of conjugation is one of the most important conjugation mechanisms
in animals (Miettinen and Leskinen, 1970; Williams, 1967). Some examples of
these glucuronide conjugates are shown in Fig. 1.13. Two animal groups which
appear to have only minimal capacity for glucuronidation are cats and fishes.
The reasons may be a reduced transferase activity in the cat, and a deficiency
in the endogenous glucuronic acid donor in the fish (Parke, 1968).
1.3.2. Sulfoconjugation
Sulfotransferases are enzymes that catalyze sulfate conjugation in various
organisms (Horkin and Stotz, 1973). The conjugation of compounds with sulfate
is common in microorganisms, plants, and animals; the subject has been reviewed
by Dodgson and Rose (1970).
The endogenous donor of the sulfate group is 3' -phosphoadenosine-5' -phosphosulfate (PAPS), which is an activated form of sulfate. O-sulfate conjugates
13
species the endogenous substrates are commonly glucuronic acid, sulfate, and
amino acids. Glucose instead of glucuronic acid, is the most common endogenous
substrate in insects and plants (Parke, 1968).
Pesticides usually require some type of phase I metabolism to produce an
-OH, -COOH, -NH2' -NHOH, or -SH site for subsequent conjugation with an
endogenous compound (Smith, 1968; Jenner and Testa, 1978). If the endogenous
compound is glucose, the conjugate is called a glucoside, and when it is glucuronic acid, it is referred to as a glucuronide. The terms that differentiate
between the exogenous and endogenous moieties of the sugar conjugate or glycoside are glycone (sugar moiety) and aglycone (exogenous portion). The other
types of conjugates do not have comparable terms to distinguish between the
exogenous and endogenous portions of any conjugate, so the term exocon has
been used to indicate the exogenous portion, and endocon to note the endogenous
moiety (Dorough, 1976).
1.3. 1. Glycoside Formation
While glucoside conjugation of xenobiotics is rare in mammals, some exceptions are reported in the literature. An example of this is the conjugation of
a xanthine oxidase inhibitor with glucose in dogs, rats, and monkeys (Duggan
et al., 1974). Conclusive evidence that pesticides undergo glucose conjugation
in mammals has yet to be presented.
In vertebrate species, many pesticides or their metabolites are conjugated
as glucuronides. Glucuronic acid does not react directly, but is present in an
active form (uridine diphosphate glucuronic acid, UDPGA), which is synthesized
enzymatically from a-glucose-6-phosphate and glucuronic acid. Conjugation
with a pesticide or its metabolite is mediated by glucuronyltransferase enzymes.
This type of conjugation is one of the most important conjugation mechanisms
in animals (Miettinen and Leskinen, 1970; Williams, 1967). Some examples of
these glucuronide conjugates are shown in Fig. 1.13. Two animal groups which
appear to have only minimal capacity for glucuronidation are cats and fishes.
The reasons may be a reduced transferase activity in the cat, and a deficiency
in the endogenous glucuronic acid donor in the fish (Parke, 1968).
1.3.2. Sulfoconjugation
Sulfotransferases are enzymes that catalyze sulfate conjugation in various
organisms (Horkin and Stotz, 1973). The conjugation of compounds with sulfate
is common in microorganisms, plants, and animals; the subject has been reviewed
by Dodgson and Rose (1970).
The endogenous donor of the sulfate group is 3' -phosphoadenosine-5' -phosphosulfate (PAPS), which is an activated form of sulfate. O-sulfate conjugates