From selenium to selenoproteins: synthesis, identity, and their role in human health.
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.
Papp
Laura Vanda
LV
Queensland Institute of Medical Research, Cancer and Cell Biology Division, Herston, QLD, Australia.
Lu
Jun
J
Holmgren
Arne
A
Khanna
Kum Kum
KK
D000818:Animals; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D012643:Selenium / Q000378:metabolism*; D051140:Selenoproteins / Q000096:biosynthesis* / Q000502:physiology*; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism
D051140:Selenoproteins; D005979:Glutathione Peroxidase; D013880:Thioredoxin-Disulfide Reductase; D012643:Selenium