title: Removal of hydrogen peroxide by thiol-specific antioxidant enzyme (TSA) is involved with its antioxidant properties. TSA possesses thiol peroxidase activity.
abstract: The thiol-specific antioxidant protein (TSA) protects glutamine synthetase from inactivation by a metal-catalyzed oxidation (MCO) system comprised of dithiothreitol (DTT)/Fe3+/O2 but not by the ascorbate/Fe3+/O2 MCO system. The removal of sulfur-centered radicals or H2O2 has been proposed as the protective mechanism of TSA. Like catalase, TSA prevents the initiation of the rapid O2 uptake phase during MCO of DTT but causes only partial inhibition when added after the reaction is well into the propagation phase. Stoichiometric studies showed that the antioxidant property of TSA is, at least in part, due to its ability to catalyze the destruction of H2O2 by the overall reaction 2 RSH + H2O2 --> RSSR + H2O. Results of kinetic studies demonstrate that the removal of H2O2 by TSA correlates with its ability to protect glutamine synthetase from inactivation. In the presence of thioredoxin, TSA is more active, whereas C170S (an active mutant of TSA in which cysteine 170 was replaced by a serine) and open reading frame 6 (a human antioxidant protein homologous to TSA with only one conserved cysteine residue) are only slightly affected. The thiol specificity of the protective activity of TSA derives from the fact that the oxidized form of TSA can be converted back to its sulfhydryl form by treatment with thiols but not by ascorbate.
authors.affiliation: Laboratory of Biochemistry and the Laboratory of Cell Signaling, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.lastname: LES Netto
authors.forename: H Z
authors.initials: HZ
authors.lastname: Chae
authors.forename: S W
authors.initials: SW
authors.lastname: Kang
authors.forename: S G
authors.initials: SG
authors.lastname: Rhee
authors.forename: E R
authors.initials: ER
authors.lastname: Stadtman
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002474:Cell-Free System; D004229:Dithiothreitol / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000378:metabolism*; D054464:Peroxiredoxins; D011506:Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D000975:Antioxidants; D011506:Proteins; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D007501:Iron; D010544:Peroxidases; C058652:thiol-dependent peroxidase; D054464:Peroxiredoxins; D002374:Catalase; D005974:Glutamate-Ammonia Ligase; D004229:Dithiothreitol