SELENIUM

Discovered by the Swedish scientist Berzelius in 1817, and named after the moon (Greek: selene).
Regarded as a toxic element until 50 years ago

1957: Shown to prevent liver necrosis in rats. From ca. 1960, Se was used in veterinary medicine. In Norway, muscular dystrophy in sheep and exudative disease in calves were virtually eliminated with the use of Se. (Exudative disease or Age-related macular degeneration AMD causes vision loss.)

1972: glutathione peroxidase identified as a Se-dependent enzyme.

1979: Keshan disease treated with Se.

1965 onwards: population studies show a link between low Se levels and increased risk of cancer and heart disease.

Selenium in biological systems (and therefore in food) is present mainly in the form of amino-acids. Se is in the oxygen series of the periodic table, along with S, and can replace S in cysteine and methionine.

Selenoproteins

Animal selenoproteins contain selenocysteine (Sec) in their primary structure.
Selenium enters the food chain through plants that incorporate it into (mostly) selenomethionine.

How are selenoproteins made?

UGA is normally a termination codon. However, in an mRNA coding for a selenoprotein, there is a stem-loop structure in the 3’ untranslated region that somehow instructs the ribosome to incorporate Sec rather than terminate the protein.

A specific tRNA molecule, tRNASerSec, with the anticodon for UGA, is charged with Ser by Ser-tRNA ligase. The Ser is then converted to selenocysteine in a reaction involving selenophosphate.

Figure
Biosynthesis of selenoproteins (proteins containing selenocystein)
A UGA is normally a termination codon. However, selenoprotein mRNA sequences contain a SECIS element (selenocystein insertion sequence) that interacts with the ribosome and makes the UGA codon encode selenocystein (Sec) instead of terminate translation. This cotranslational insertion is dependent on interaction with a specific tRNA.

Biological functions of selenium

Selenium, as selenocysteine, is an integral component of two important enzymes:

• glutathione peroxidase
• iodothyronine deiodinase (conversion of T4 to T3)

It also occurs in selenoprotein P and other selenoproteins.

It protects against toxic metals - Hg, As, Cd.

It has a structural role in sperm.

Other selenoproteins

• Glutathione peroxidase – GSHPx-1, 2, 3, 4
• Thioredoxin reductase (reduces many proteins, e.g. insulin)
• Selenophosphate synthetase
• Selenoprotein W