Regulation of Redox Signaling by Selenoproteins
Wayne Chris Hawkes
&
Zeynep Alkan
Received: 10 February 2010 / Accepted: 12 February 2010 /
Published online: 20 March 2010
#
The Author(s) 2010. This article is published with open access at Springerlink.com
Abstract The unique chemistry of oxygen has been both a resource and threat for life on
Earth for at least the last 2.4 billion years. Reduction of oxygen to water allows extraction
of more metabolic energy from organic fuels than is possible through anaerobic glycolysis.
On the other hand, partially reduced oxygen can react indiscriminately with biomolecules to
cause genetic damage, disease, and even death. Organisms in all three superkingdoms of
life have developed elaborate mechanisms to protect against such oxidative damage and to
exploit reactive oxygen species as sensors and signals in myriad processes. The sulfur
amino acids, cysteine and methionine, are the main targets of reactive oxygen species in
proteins. Oxidative modifications to cysteine and methionine can have profound effects on
aprotein’s activity, structure, stability, and subcellular localization. Non-reversible
oxidative modifications (oxidative damage) may contribute to molecular, cellular, and
organismal aging and serve as signals for repair, removal, or programmed cell death.
Reversible oxidation events can function as transient signals of physiological status,
extracellular environment, nutrient availability, metabolic state, cell cycle phase, immune
function, or sensory stimuli. Because of its chemical similarity to sulfur and stronger
nucleophilicity and acidity, selenium is an extremely efficient catalyst of reactions between
sulfur and oxygen. Most of the biological activity of selenium is due to selenoproteins
containing selenocysteine, the 21st genetically encoded protein amino acid. The most
abundant selenoproteins in mammals are the glutathione peroxidases (five to six genes) that
reduce hydrogen peroxide and lipid hydroperoxides at the expense of glutathione and serve
to limit the strength and duration of reactive oxygen signals. Thioredoxin reductases (three
genes) use nicotinamide adenine dinucleotide phosphate to reduce oxidized thioredoxin and
its homologs, which regulate a plethora of redox signaling events. Methionine sulfoxide
reductase B1 reduces methionine sulfoxide back to methionine using thioredoxin as a
Biol Trace Elem Res (2010) 134:235–251
DOI 10.1007/s12011-010-8656-7
The authors have no financial or other conflicting interest in any product or service mentioned in this article.
W. C. Hawkes (*)
:
Z. Alkan
USDA Agricultural Research Service, Western Human Nutrition Research Center,
University of California at Davis, Davis, USA
e-mail: wayne.hawkes@ars.usda.gov
Z. Alkan
e-mail: zeynep.alkan@ars.usda.gov