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.

Identification and localization of glutathione S-transferase as a potential target enzyme in Brugia species

“…All these studies indicate that glutathione-binding proteins in worms are predominantly associated with metabolic and reproductive sites. The identi®cation of a speci®c rat GST isozyme that is abundant in spermatogenic tubules and exhibits high GSH-peroxidase activity with pyrimidine hydroperoxides as substrates suggests that GSTs may be important to the ®delity of DNA replication by detoxifying pyrimidine hydroperoxides (Tan et al 1986). …”

Ionizing radiation-induced mutagenesis

“…They may also be involved in forming protein DNA cross-links (Teebor et al, 1984;Simic & Dizdaroglu, 1985). These hydroperoxides may be reconstituted to the original base through the action of glutathione dependent enzymatic processes thus limiting the damage (Tan et al, 1986;Edgren, 1987).…”

The separation of glutathione transferase subunits by using reverse-phase high-pressure liquid chromatography

“…1. 18) are enzymes associated with the detoxication of electrophiles (Mannervik, 1985;Ketterer et al, 1986), the reduction of fatty acid hydroperoxides and pyrimidine hydroperoxides (Tan et al, 1986), the isomerization of prostaglandins (Christ-Hazelhof & Nutgeren, 1979) and non-covalent binding affinity for a range of compounds with hydrophobic moieties (Ketterer et al, 1978).…”