Glutathione peroxidase family – an evolutionary overview

Abstract

Glutathione peroxidases (EC 1.11.1.9 and EC 1.11.1.12) catalyze the reduction of H2O2 or organic hydroperoxides to water or corresponding alcohols using reduced glutathione. Some glutathione peroxidase isozymes have a selenium‐dependent glutathione peroxidase activity and present a selenocysteine encoded by the opal TGA codon. In the present study, insights into the evolution of the whole glutathione peroxidase gene family were obtained after a comprehensive phylogenetic analysis using the improved number of glutathione peroxidase sequences recorded in the PeroxiBase database (http://peroxidase.isb-sib.ch/index.php). The identification of a common ancestral origin for the diverse glutathione peroxidase clusters was not possible. The complex relationships and evolutionary rates of this gene family suggest that basal glutathione peroxidase classes, present in all kingdoms, have originated from independent evolutionary events such as gene duplication, gene losses, lateral gene transfer among invertebrates and vertebrates or plants. In addition, the present study also emphasizes the possibility of some members being submitted to strong selective forces that probably dictated functional convergences of taxonomically distant groups.

The role of the antioxidant system during intense endurance exercise: lessons from migrating birds

“…Several important GPxs that act as antioxidant enzymes are selenoproteins, and have a selenocystine (Sec) residue at their active site (Johansson et al, 2005). Four major selenium-dependent GPxs have been identified in mammals and birds in different tissues, and in distinct subcellular locations (Gibson et al, 2014;Johansson et al, 2005;Kong et al, 2003;Margis et al, 2008). GPx1 is found in red blood cells, the liver, lung and kidney and is restricted to the cytosol, nucleus and mitochondria.…”

“…Birds and mammals are able to synthesize these antioxidants, which act as nucleophiles for RS. GSH is present at relatively high concentrations in cells, and directly acts to neutralize H 2 O 2 and hydroperoxides, which are abundant RS in migrating birds (Costantini, 2014;Deponte, 2013;Halliwell and Gutteridge, 2007;Kaminśki et al, 2009;Margis et al, 2008). Unlike other reactions between sacrificial molecules and RS, the GSH reaction is catalyzed by the antioxidant enzyme glutathione peroxidase (GPx, see below), which means that GSH and GPx must be present at high concentrations for GSH to be effective (Fig.…”

Comparison of the seleno-transcriptome expression between human non-cancerous mammary epithelial cells and two human breast cancer cell lines

“…In mammalian tissues, there are five major Se-dependent GPX isozymes: GPX1 are located in the cytosol, nucleus and mitochondria of erythrocytes, and the liver, lung and kidney; GPX2 in the cytosol and nucleus, and the gastrointestinal tract; GPX3 in the mitochondria of several organs, including the kidney, lung, epididymis, breast, heart and muscle; GPX4 in the nucleus, cytosol and mitochondria of various tissues; and GPX6 in the olfactory epithelium. By contrast, GPX5, secreted in the epididymis, does not have Sec at the active site, and GPX7, recently described as a novel phospholipid hydroperoxide glutathione peroxidase, incorporates cysteine instead of Sec in the conserved catalytic motif (31). The best characterized member of the GPX family is GPX1, which uses reducing equivalents from glutathione to detoxify peroxides (32) and is decreased in tumor cells compared with their normal counterparts (33).…”

Reactive Oxygen Species in Inflammation and Tissue Injury

“…There are four seleniumdependent GPx enzymes (GPx1-4) in mammalian tissue with a wide tissue distribution (270). GPx enzymes are tetrameric 85 kDa protein and carry four atoms of selenium bound in their catalytic core.…”