PRINCIPLES OF TOXICOLOGY

oth of which are suitable for conjugation, if the metabolites are not first excreted as the phase I products
(Figure 3.10).
Epoxide hydrolase activity is predominantly microsomal, but an enzyme is also present in the
cytosol.
Most hydrolyses occur to a significant extent in tissues other than liver. Their quantitative
importance is variable, depending on the chemical challenge. One significant extrahepatic location of
esterases is in the blood (plasma and erythrocytes), and of great concern is the enzyme normally
responsible for the hydrolysis of acetylcholine. Blockade of this enzyme is the mode of action of many
insecticides and “ nerve gases.”
Figure 3.10 Hydrolytic and reductive phase I reactions.
3.2 BIOTRANSFORMATION REACTIONS 71