Elsevier

Advances in Nutrition

Volume 2, Issue 2, 1 March 2011, Pages 122-128
Advances in Nutrition

Biosynthesis of Selenocysteine, the 21st Amino Acid in the Genetic Code, and a Novel Pathway for Cysteine Biosynthesis

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ABSTRACT

The biosynthetic pathway for selenocysteine (Sec), the 21st amino acid in the genetic code whose codeword is UGA, was recently determined in eukaryotes and archaea. Sec tRNA, designated tRNA[Ser]Sec, is initially aminoacylated with serine by seryl-tRNA synthetase and the resulting seryl moiety is converted to phosphoserine by O-phosphoseryl-tRNA kinase to form O-phosphoseryl-tRNA[Ser]Sec. Sec synthase (SecS) then uses O-phosphoseryl-tRNA[Ser]Sec and the active donor of selenium, selenophosphate, to form Sec-tRNA[Ser]Sec. Selenophosphate is synthesized from selenide and ATP by selenophosphate synthetase 2 (SPS2). Sec was the last protein amino acid in eukaryotes whose biosynthesis had not been established and the only known amino acid in eukaryotes whose biosynthesis occurs on its tRNA. Interestingly, sulfide can replace selenide to form thiophosphate in the SPS2-catalyzed reaction that can then react with O-phosphoseryl-tRNA[Ser]Sec in the presence of SecS to form cysteine-(Cys-)tRNA[Ser]Sec. This novel pathway of Cys biosynthesis results in Cys being decoded by UGA and replacing Sec in normally selenium-containing proteins (selenoproteins). The selenoprotein, thioredoxin reductase 1 (TR1), was isolated from cells in culture and from mouse liver for analysis of Cys/Sec replacement by MS. The level of Cys/Sec replacement in TR1 was proportional to the level of selenium in the diet of the mice. Elucidation of the biosynthesis of Sec and Sec/Cys replacement provides novel ways of regulating selenoprotein functions and ultimately better understanding of the biological roles of dietary selenium.

Abbreviations

SECIS
Sec insertion sequence
Um34
methyl group located on the 2′-hydroxylribose at wobble position of selenocysteine tRNA

Cited by (0)

Supported by the Intramural Research Program of the NIH, National Cancer Institute, and Center for Cancer Research (to D.L.H.) and by NIH grants awarded to V.N.G.

Author disclosures: A. Turanov, X-M. Xu, B. A. Carlson, M-H. Yoo, V. N. Gladyshev, and D. L. Hatfield, no conflicts of interest.

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Present address: GeneCopoeia, Inc., Rockville, MD 20850.