Review article
Synthesis and decoding of selenocysteine and human health
Rachel L. Schmidt
; Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Ill, USA
Miljan Simonović
orcid.org/0000-0002-1576-2222
; Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Ill, USA
Abstract
Selenocysteine, the 21st amino acid, has been found in
25 human selenoproteins and selenoenzymes important
for fundamental cellular processes ranging from selenium
homeostasis maintenance to the regulation of the overall
metabolic rate. In all organisms that contain selenocysteine,
both the synthesis of selenocysteine and its incorporation
into a selenoprotein requires an elaborate synthetic and
translational apparatus, which does not resemble the canonical
enzymatic system employed for the 20 standard
amino acids. In humans, three synthetic enzymes, a specialized
elongation factor, an accessory protein factor, two
catabolic enzymes, a tRNA, and a stem-loop structure in
the selenoprotein mRNA are critical for ensuring that only
selenocysteine is attached to selenocysteine tRNA and that
only selenocysteine is inserted into the nascent polypeptide
in response to a context-dependent UGA codon. The
abnormal selenium homeostasis and mutations in selenoprotein
genes have been causatively linked to a variety of
human diseases, which, in turn, sparked a renewed interest
in utilizing selenium as the dietary supplement to either
prevent or remedy pathologic conditions. In contrast, the
importance of the components of the selenocysteine-synthetic
machinery for human health is less clear. Emerging
evidence suggests that enzymes responsible for selenocysteine
formation and decoding the selenocysteine UGA
codon, which by extension are critical for synthesis of the
entire selenoproteome, are essential for the development
and health of the human organism.
Keywords
Hrčak ID:
94955
URI
Publication date:
15.12.2012.
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