HUMAN THIOREDOXIN REDUCTASE DIRECTLY REDUCES LIPID HYDROPEROXIDES BY NADPH AND SELENOCYSTINE STRONGLY STIMULATES THE REACTION VIA CATALYTICALLY GENERATED SELENOLS

Human placenta thioredoxin reductase (HP-TR) in the presence of NADPH- catalyzed reduction of hydroperoxy-(5Z),(8Z),11(Z),13(E)-eicosatetraen oic acid ((15S)-HPETE) into the corresponding alcohol ((15S)-HETE). In cubation of 50 nM HP-TR and 0.5 mM NADPH with 300 mu M 18-HPETE for 5 min resulted in formation of 16.5 mu M 15-HETE. After 60 min, 74.7 mu M 15-HPETE was reduced. The rate of the reduction of 15-HPETE by the H P-TR/NADPH peroxidase system was increased 8-fold by the presence of 2 .5 mu M selenocystine, a diselenide amino acid. In this case, 15-HPETE was catalytically reduced by the selenol amino acid, selenocysteine, generated from the diselenide by the HP-TR/NADPH system. To a smaller extent, selenodiglutathione or human thioredoxin also potentiated the reduction of 15-HPETE by HP-TR. Hydrogen peroxide and 15-HPETE were re duced at approximately the same rate by HP-TR, thioredoxin, and seleno cystine. In contrast, t-butyl hydroperoxide was reduced at a 10-fold l ower rate. Our data suggest two novel pathways for the reduction and d etoxification of lipid hydroperoxides, hydrogen peroxide, and organic hydroperoxides, i.e. the human thioredoxin reductase-dependent pathway and a coupled reduction in the presence of selenols or selenide resul ting from the reduction of selenocystine or selenodiglutathione.