Selenocysteine Biosynthesis and the Replacement of Selenocysteine with Cysteine in the Pathway

The biosynthetic pathway of selenocysteine (Sec), the 21st amino acid in the genetic code, has been established in eukaryotes and archaea using comparative genomic and experimental approaches. In addition, cysteine (Cys) was found to arise in place of selenocysteine in thioredoxin reductase (TR) in NIH 3T3 cells and in mice. An analysis of the selenocysteine biosynthetic pathway demonstrated that replacement of selenide with sulfide in generating the active cysteine donor, thiophosphate, resulted in cysteine being donated to the acceptor molecule, which is likely dehydroalanyl-tRNA[Ser]Sec, yielding Cys-tRNA[Ser]Sec. The identification of the pathways for biosynthesis of selenocysteine and cysteine in mammals is discussed in this chapter.