title: Phospholipid hydroperoxide glutathione peroxidase (PHGPx): more than an antioxidant enzyme?
abstract: The family of glutathione peroxidases encompasses, as far, three tetrameric glutathione peroxidases (GPx) and the monomeric PHGPx. Although the overall homology between tetrameric enzymes and PHGPx is less than 30%, a pronounced similarity has been detected on clusters involved in the active site and a common catalytic triad (selenocysteine glutamine and tryptophan) has been defined by structural and kinetic data. A major peculiar feature of the reaction catalyzed by PHGPx is the possibility to accommodate large lipophilic substrates. This accounts for the observed dramatic antiperoxidant effect and the synergism with vitamin E. Moreover, the reduction of lipid hydroperoxides accounts also for the observed modulation of cycloxygenase and inhibition of 15-lipoxygenase. On the other hand, structural and kinetic data indicate that also the specificity of PHGPx for the donor substrate is not restricted to GSH and the recent observation the PHGPx binds to specific mitochondrial proteins, from which it is released by ionic strength and thiols, suggests a possible fole of this selenoenzyme in catalyzing the specific oxidation of protein thiols, thus modulating the activity of cellular regulatory elements. On this light, the selenium mojety of PHGPx, reacting much faster that thiols with a peroxide, and then oxidizing specific protein thiols, would channel the oxidation toward protein targets, thus providing, by protein-protein interaction, the specificity of the redox transition.
authors.affiliation: Department of Biological Chemistry, University of Padova, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Ursini
authors.forename: M
authors.initials: M
authors.lastname: Maiorino
authors.forename: A
authors.initials: A
authors.lastname: Roveri
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase
chemical_list: D000975:Antioxidants; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase