Page 173 - The Toxicology of Fishes

4

Biotransformation in Fishes

Daniel Schlenk, Malin Celander, Evan P. Gallagher, Stephen George,
Margaret James, Seth W. Kullman, Peter van den Hurk, and Kristie Willett

CONTENTS
Introduction............................................................................................................................................154
Phase I Reactions...................................................................................................................................154
Oxidation ......................................................................................................................................154
Cytochrome P450 Family of Drug Metabolizing Enzymes ..............................................154
Flavin-Containing Monooxygenases..................................................................................175
Monoamine Oxidases .........................................................................................................178
Alcohol and Aldehyde Dehydrogenases ............................................................................178
Peroxidases .........................................................................................................................179
Aldehyde Oxidase...............................................................................................................179
Reductases ....................................................................................................................................179
DT Diaphorase....................................................................................................................179
Azo- and Nitroreductases ...................................................................................................179
Hydrolysis.....................................................................................................................................180
Epoxide Hydrolase..............................................................................................................180
Carboxylesterases ...............................................................................................................182
Phase II Enzymes...................................................................................................................................183
UDP-Glucuronosyltransferases ....................................................................................................183
Overview.............................................................................................................................183
UGT Gene Structure...........................................................................................................184
Reactions and Substrate Specificity ...................................................................................185
Enzymology of Piscine UGTs............................................................................................187
Tissue Distribution..............................................................................................................188
Regulation of UGTs ...........................................................................................................188
Inhibition of UGTs .............................................................................................................189
Glutathione S-Transferases...........................................................................................................190
Overview.............................................................................................................................190
GST Gene Structure ...........................................................................................................191
Reactions and Substrate Specificity ...................................................................................193
Fish GST and Oxidative Stress ..........................................................................................194
Tissue Distribution..............................................................................................................196
Regulation of GSTs............................................................................................................197
Inhibition of GSTs..............................................................................................................199
Sulfotransferase ............................................................................................................................199
Overview.............................................................................................................................199
Gene Structure of SULT.....................................................................................................201
Piscine SULTs.....................................................................................................................203
Reactions and Substrate Specificity ...................................................................................203
Tissue Distribution..............................................................................................................204
Regulation of SULT............................................................................................................204
Inhibition of SULT .............................................................................................................205
Activation of SULT ............................................................................................................205

153