Positive Health Online

Abstract

PAYNE and COLLEAGUES, 1. Department of Biochemistry, 89 Beaumont Ave, Given Building Room B413, Burlington, VT 05405, United States; 2. Department of Chemistry, St. Michael's College, 1 Winooski Park, Colchester, VT 05439, United States; 3. Division of Genetics, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, United States; 4. Department of Biochemistry, 89 Beaumont Ave, Given Building Room B413, Burlington, VT 05405, United States. Robert.Hondal@uvm.edu conducted research and comparatively analyzed the oxidation reactions underlying the role of the substitution of sulphur and selenium for oxygen and selenium in 2-selenouridine.

Background

Selenium is present in proteins in the form of selenocysteine, where this amino acid serves catalytic oxidoreductase functions. The use of selenocysteine in nature is strongly associated with redox catalysis. However, selenium is also found in a 2-selenouridine moiety at the wobble position of tRNAGlu, tRNAGln and tRNALys.

Methodology

It is thought that the modifications of the wobble position of the tRNA improves the selectivity of the codon-anticodon pair as a result of the physico-chemical changes that result from substitution of sulphur and selenium for oxygen. Both selenocysteine and 2-selenouridine have widespread analogs, cysteine and thiouridine, where sulphur is used instead. To examine the role of selenium in 2-selenouridine, we comparatively analyzed the oxidation reactions of sulphur-containing 2-thiouracil-5-carboxylic acid (s2c5Ura) and its selenium analog 2-selenouracil-5-carboxylic acid (se2c5Ura) using 1H-NMR spectroscopy, 77Se-NMR spectroscopy, and liquid chromatography-mass spectrometry.

Results

Treatment of s2c5Ura with hydrogen peroxide led to oxidized intermediates, followed by irreversible desulfurization to form uracil-5-carboxylic acid (c5Ura). In contrast, se2c5Ura oxidation resulted in a diselenide intermediate, followed by conversion to the seleninic acid, both of which could be readily reduced by ascorbate and glutathione. Glutathione and ascorbate only minimally prevented desulfurization of s2c5Ura, whereas very little deselenization of se2c5Ura occurred in the presence of the same antioxidants. In addition, se2c5Ura but not s2c5Ura showed glutathione peroxidase activity, further suggesting that oxidation of se2c5Ura is readily reversible, while oxidation of s2c5Ura is not.

Conclusion

The results of the study of these model nucleobases suggest that the use of 2-selenouridine is related to resistance to oxidative inactivation that otherwise characterizes 2-thiouridine. As the use of selenocysteine in proteins also confers resistance to oxidation, our findings suggest a common mechanism for the use of selenium in biology.

References

Payne NC1, Geissler A1, Button A1, Sasuclark AR2, Schroll AL2, Ruggles EL1, Gladyshev VN3, Hondal RJ4. Comparison of the redox chemistry of sulfur- and selenium-containing analogs of uracil. Free Radic Biol Med; 104:249-261. doi: 10.1016/j.freeradbiomed.2017.01.028. Epub Jan 17 2017 . Mar 2017.