Glutathione peroxidases

Abstract

The present state of knowledge on glutathione peroxidases (GPxs) is reviewed with particular emphasis on general catalytic principles and the biology of mammalian glutathione peroxidases. GPxs make up a ubiquitous family of proteins defined by sequence homology, the common functional denominator being their ability to reduce hydroperoxides by thiols. Catalysis is mediated by an active-site selenocysteine or cysteine. Eight distinct GPxs have been identified in mammals, five of them being selenoproteins in man. While glutathione specificity prevails in vertebrate GPxs, thioredoxins or related redoxins appear to be common substrates in plant, bacterial and protist GPxs. Specific reactions of GPxs with other protein thiols are also observed. The basic catalytic scheme allows the enzymes to adopt diversified biological roles ranging from defence against peroxide challenge, redox regulation of metabolic processes and transcription, apoptosis to cellular differentiation. The roles of the individual mammalian GPxs are discussed in the light of distinct substrate specificities, distribution, subcellular compartmentation, expression patterns and data from inverse genetics. It is outlined that the multiple coexisting GPxs and functionally related peroxiredoxins likely build up a system of enzymes that, with discrete functional overlap, complement each other in meeting specific biological tasks far beyond fighting oxidative stress.