PURIFICATION AND CHARACTERIZATION OF HEPATIC GLUTATHIONE TRANSFERASESFROM AN INSECTIVOROUS MARSUPIAL, THE BROWN ANTECHINUS (ANTECHINUS-STUARTII)

1. Five unique glutathione transferase isoenzymes were purified from t he hepatic cytosol of an insectivorous marsupial, the brown antechinus . The purified GSTs were characterized by structural and catalytic pro perties including apparent molecular weight and isoelectric point, spe cificity rewards model substrates, kinetic parameters, sensitivity to inhibitors and cross-reactivity with antisera raised against human GST s. 2. An alpha class GST, Antechinus GST 1-1, predominated in the hepa tic cytosol, representing 71% of the total GST purified. The substrate specificity of Antechinus GST 1-1 was similar to that of other alpha class GSTs, particularly with respect to its high activity with cumene hydroperoxide. The mu class was represented by three GST isoenzymes, Antechinus GST 3-3, GST 3-4 and GST 4-4. These isoenzymes represented 8, 2 and 10% of the total GST purified respectively. A single GST, Ant echinus GST 22, belonged to the pi class of GSTs and represented 12% o f the total GST purified. The hepatic GST isoenzyme ratio (by class) o bserved in the brown antechinus was more similar to that observed in t he human than in rat. 3. A previous study investigating a herbivorous marsupial, the brushtail possum (Trichosurus vulpecula) also identifie d a predominant hepatic GST belonging to the alpha class and displayin g peroxidase activity. The evolutionary conservation of a similar pred ominant GST isoenzyme in these marsupials suggests that they play an i mportant role in the detoxication metabolism of these unique mammals.