PMID:7744824
| Citation |
Björnstedt, M, Hamberg, M, Kumar, S, Xue, J and Holmgren, A (1995) Human thioredoxin reductase directly reduces lipid hydroperoxides by NADPH and selenocystine strongly stimulates the reaction via catalytically generated selenols. J. Biol. Chem. 270:11761-4 |
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| Abstract |
Human placenta thioredoxin reductase (HP-TR) in the presence of NADPH-catalyzed reduction of (15S)-hydroperoxy-(5Z),(8Z),11(Z),13(E)-eicosatetraenoic acid ((15S)-HPETE) into the corresponding alcohol ((15S)-HETE). Incubation of 50 nM HP-TR and 0.5 mM NADPH with 300 microM 15-HPETE for 5 min resulted in formation of 16.5 microM 15-HETE. After 60 min, 74.7 microM 15-HPETE was reduced. The rate of the reduction of 15-HPETE by the HP-TR/NADPH peroxidase system was increased 8-fold by the presence of 2.5 microM 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 reduced at approximately the same rate by HP-TR, thioredoxin, and selenocystine. In contrast, t-butyl hydroperoxide was reduced at a 10-fold lower rate. Our data suggest two novel pathways for the reduction and detoxification 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 resulting from the reduction of selenocystine or selenodiglutathione. |
| Links | |
| Keywords |
Catalysis; Cystine/analogs & derivatives; Cystine/metabolism; Glutathione/analogs & derivatives; Glutathione/pharmacology; Glutathione Transferase/metabolism; Humans; Hydrogen Peroxide/metabolism; Hydroxyeicosatetraenoic Acids/metabolism; Leukotrienes/metabolism; Lipid Peroxidation/drug effects; Lipid Peroxides/metabolism; MAP Kinase Kinase 1; Mitogen-Activated Protein Kinase Kinases; Models, Biological; NADP/metabolism; Organoselenium Compounds/metabolism; Organoselenium Compounds/pharmacology; Oxidation-Reduction; Peroxides/metabolism; Placenta/enzymology; Protein-Serine-Threonine Kinases/chemistry; Protein-Serine-Threonine Kinases/metabolism; Protein-Tyrosine Kinases/chemistry; Protein-Tyrosine Kinases/metabolism; Selenocysteine/metabolism; Thioredoxin-Disulfide Reductase/pharmacology; Thioredoxins/pharmacology; tert-Butylhydroperoxide |
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