The requirement of the trace element selenium for life and its beneficial role in human health has been known for several decades. This is attributed to low molecular weight selenium compounds, as well as to its presence within at least 25 proteins, named selenoproteins, in the form of the amino acid selenocysteine (Sec). Incorporation of Sec into selenoproteins employs a unique mechanism that involves decoding of the UGA codon. This process requires multiple features such as the selenocysteine insertion sequence (SECIS) element and several protein factors including a specific elongation factor EFSec and the SECIS binding protein 2, SBP2. The function of most selenoproteins is currently unknown; however, thioredoxin reductases (TrxR), glutathione peroxidases (GPx) and thyroid hormone deiodinases (DIO) are well characterised selenoproteins involved in redox regulation of intracellular signalling, redox homeostasis and thyroid hormone metabolism. Recent evidence points to a role for selenium compounds as well as selenoproteins in the prevention of some forms of cancer. A number of clinical trials are either underway or being planned to examine the effects of selenium on cancer incidence. In this review we describe some of the recent progress in our understanding of the mechanism of selenoprotein synthesis, the role of selenoproteins in human health and disease and the therapeutic potential of some of these proteins.

https://www.liebertpub.com/doi/pdf/10.1089/ars.2007.1528

From selenium to selenoproteins: Synthesis, identity, and their role in human health

Biomarkers of free radical damage: Applications in experimental animals and in humans

Selenium is an essential micronutrient with important functions in human health and relevance to several pathophysiological conditions. The biological effects of selenium are largely mediated by se...

https://www.physiology.org/doi/pdf/10.1152/physrev.00039.2013

Selenoproteins: molecular pathways and physiological roles.

There are several proteins in mammalian cells that can metabolize hydrogen peroxide and lipid hydroperoxides. These proteins include four selenium-containing glutathione peroxidases that are found in different cell fractions and tissues of the body. This review considers the structure and distribution of the selenoperoxidases and how this relates to their biological function. The functions of the selenoperoxidases were originally studied in systems where their activity was manipulated by changing dietary selenium levels. More recently, molecular techniques have allowed overexpression of selenoperoxidases in cell lines and animals. Additionally, cellular glutathione peroxidase knockout mice have been used to investigate the functions of this protein. From this work it is clear that the selenoperoxidases are involved in cell antioxidant systems. However, they also have more subtle functions in ensuring the regulation and formation of arachadonic acid metabolites that are derived from hydroperoxide intermediates. The range of biological processes, which are potentially dependent on optimal selenoperoxidase activity in mammals, emphasises the importance of achieving adequate selenium intake in the diet.

The glutathione peroxidases.

Nutrient reference values for Australia and New Zealand: Including recommended dietary intakes

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840210242

P. Reid Lyons

Papers

Pathogenesis of diquat-induced liver necrosis in selenium-deficient rats: Assessment of the roles of lipid peroxidation and selenoprotein P

Differential regulation of rat liver selenoprotein mRNAs in selenium deficiency.

Effect of selenium on selenoprotein P expression in cultured liver cells.