Page 177 - The Toxicology of Fishes

Biotransformation in Fishes 157

Heteroatom oxygenation

O
C S CH
H 3 3 C S CH
H 3 3

Oxidative deamination

O
CH 2 CH NH 2 CH C
+ NH
2
3
CH 3 CH 3
Oxidative desulfuration
O
S S
C H O P OC H
2 5
2 5
C H O P OC H
2 5
2 5
O
S

NO 2
NO 2
Paraoxon
Parathion
FIGURE 4.2B Examples of reactions catalyzed by cytochrome P450.

Oxidative dehalogenation

Cl O
Cl

Cl C C Cl C CH 2
H H 2
Cl Cl
1,1,2–Trichloroethane Chloroacetylchloride

FIGURE 4.2C Examples of reactions catalyzed by cytochrome P450.
The reaction begins with the transfer of electrons from NAD(P)H to NADPH–cytochrome P450 reductase
in the microsomal system (Figure 4.1). The active site of CYPs is generally a noncovalently bound heme
iron in the form of protoporphyrin IX (Gonzalez and Gelboin, 1993; Henne et al., 1992). CYP-mediated
reactions include aliphatic and aromatic carbon hydroxylation, epoxidation, heteroatom dealkylations,
heteroatom oxygenation, deamination, desulfuration, and dehalogenation (Figure 4.2).
The reaction cycle is initiated when the substrate binds to the oxidized (Fe ) CYP complex and
+3
facilitates an electron transfer from NADPH to the complex. Oxygen then binds to the reduced CYP
complex with coordination to iron trans to thiolate. The second electron is contributed by either