Selenocysteine

Selenocysteine, abbreviated Sec and sometimes called the 21st amino acid, is the selenium-containing analog of cysteine. In its side chain the sulfur atom is replaced by selenium, giving a selenol group that is more reactive than a thiol. Sec is incorporated into certain proteins during translation, conferring unique catalytic properties to selenoproteins involved in redox biology and metabolic regulation.

In most organisms, the UGA codon, which normally signals translation termination, is recoded to insert selenocysteine when a dedicated structural element called a SECIS (selenocysteine insertion sequence) is present in the mRNA, typically in the 3' untranslated region. The Sec incorporation machinery varies by domain: in bacteria, a specialized tRNA^Sec is charged with serine and converted to Sec-tRNA^Sec by the enzyme SelA, using selenophosphate supplied by SelD, with the process directed by SelB. In archaea and eukaryotes, Sec-tRNA^Sec is formed from Ser-tRNA^Sec via phosphoryl transfer by PSTK and conversion by SepSecS, aided by SECIS-binding proteins such as SBP2 and eukaryotic elongation factors.

Selenoproteins containing Sec play roles in antioxidant defense, thyroid hormone metabolism, and redox regulation. Examples include glutathione peroxidases, thioredoxin reductases, and deiodinases, among others. The incorporation of Sec is a finely regulated feature of gene expression and varies among organisms, reflecting evolutionary adaptations to selenium availability and redox requirements.

Discovery of selenocysteine occurred in the mid-20th century, with subsequent work establishing its genetic encoding via the SECIS element and specialized translation factors. Selenium biology and selenoprotein function remain active areas of research with implications for nutrition and human health.