Thymine hydroperoxide, a substrate for rat Se‐dependent glutathione peroxidase and glutathione transferase isoenzymes

Abstract

The thymine hydroperoxide, 5-hydroperoxymethyluracil, is a substrate for Se-dependent glutathione (GSH) peroxidase and the Se-independent GSH peroxidase activity associated with the GSH transferase fraction. These enzymes may contribute to repair mechanisms for damage caused by oxygen radicals. GSH transferases 1-1, 2-2, 3-3, 4-4, 6-6, and 7-7 [(1984) Biochem. Pharmacol. 33, 2539-2540] are shown to differ considerably in their ability to utilize this substrate. For example, high activity is found in GSH transferase 6-6 which is the major isoenzyme in spermatogenic tubules where DNA synthesis is so active and faithful DNA replication so important. The activity of the purified GSH transferase isoenzymes towards 5-hydroperoxymethyluracil is comparable with their activity towards other endogenous substrates related to cellular peroxidation such as linoleate hydroperoxide and 4-hydroxynon-2-enal or biologically important xenobiotic metabolites such as benzo(a)pyrene-7,8-diol-9,10-oxide.