Selenium and selenocysteine: roles in cancer, health, and development

Hatfield, Dolph L.; Tsuji, Petra A.; Carlson, Bradley A.; Gladyshev, Vadim N.

doi:10.1016/j.tibs.2013.12.007

Cited by 574 publications

(343 citation statements)

References 89 publications

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“…Selenium is incorporated into proteins via the amino acid selenocysteine (Sec or U), which is structurally similar to cysteine yet more reactive (2). Selenoproteins exploit Sec to catalyze a wide range of electron-transfer reactions (3).…”

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confidence: 99%

Redox active motifs in selenoproteins

Lutz

Pepelyayeva

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Selenoproteins use the rare amino acid selenocysteine (Sec) to act as the first line of defense against oxidants, which are linked to aging, cancer, and neurodegenerative diseases. Many selenoproteins are oxidoreductases in which the reactive Sec is connected to a neighboring Cys and able to form a ring. These Sec-containing redox motifs govern much of the reactivity of selenoproteins. To study their fundamental properties, we have used 77 Se NMR spectroscopy in concert with theoretical calculations to determine the conformational preferences and mobility of representative motifs. This use of 77 Se as a probe enables the direct recording of the properties of Sec as its environment is systematically changed. We find that all motifs have several ring conformations in their oxidized state. These ring structures are most likely stabilized by weak, nonbonding interactions between the selenium and the amide carbon. To examine how the presence of selenium and ring geometric strain governs the motifs' reactivity, we measured the redox potentials of Sec-containing motifs and their corresponding Cys-only variants. The comparisons reveal that for C-terminal motifs the redox potentials increased between 20-25 mV when the selenenylsulfide bond was changed to a disulfide bond. Changes of similar magnitude arose when we varied ring size or the motifs' flanking residues. This suggests that the presence of Sec is not tied to unusually low redox potentials. The unique roles of selenoproteins in human health and their chemical reactivities may therefore not necessarily be explained by lower redox potentials, as has often been claimed.

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mentioning

confidence: 99%

Redox active motifs in selenoproteins

Lutz

Pepelyayeva

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…A high activity of these enzymes has been demonstrated in the thyroid tissue; however, in order to maintain iodine metabolism, catalysed by deiodinases, and at an appropriate level, low activity of these enzymes will be enough, much lower than of other selenoproteins in the pathways of the metabolic turnover of proteins, fats, and amino acids [34,77,78]. Therefore, neither the concentration of selenium nor the concentrations of selenium-containing proteins directly influence the selenium content in the thyroid and the activity of selenoproteins contained in the TG [69,79].…”

Section: Prace Poglądowementioning

confidence: 99%

“…Wykazano wysoką aktywność tych enzymów w obrębie tkanki tarczycowej, jednakże do utrzymania katalizowanego przez dejodynazy metabolizmu jodu, na odpowiednim poziomie wystarczy ich niewielka aktywność, znacznie mniejsza niż innych selenoprotein w szlakach metabolicznych przemian białek, tłuszczów i aminokwasów [34,77,78]. A zatem stężenie selenu lub zawierających go białek w surowicy nie znajduje bezpośredniego przełożenia na zawartość selenu w tarczycy i aktywność zawartych w niej selenoprotein [69,79].…”

Section: Prace Poglądoweunclassified

The role of selenium in thyroid gland pathophysiology

Stuss¹,

Michalska-Kasiczak

Sewerynek³

2017

Endokrynologia Polska

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It is now assumed that proper functioning of the thyroid gland (TG), beside iodine, requires also a number of elements, including selenium, iron, zinc, copper, and calcium. In many cases, only an adequate supply of one of these microelements (e.g. iodine) may reveal symptoms resulting from deficits of other microelements (e.g. iron or selenium). Selenium is accounted to the trace elements of key importance for homeostasis of the human system, in particular, for the proper functioning of the immune system and the TG. Results of epidemiological studies have demonstrated that selenium deficit may affect as many as one billion people in many countries all over the world. A proper sequence of particular supplementations is also worth emphasising for the significant correlations among the supplemented microelements. For example, it has been demonstrated that an excessive supplementation of selenium may enhance the effects of iodine deficit in endemic regions, while proper supplementation of selenium in studied animals may alleviate the consequences of iodine excess, preventing destructive-inflammatory lesions in the TG. This paper is a summary of the current knowledge on the role of selenium in the functionality of the TG.

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“…Among the nutrients obtained from the diet, it is known that selenium (Se) is important for healthy human metabolism and that it is involved in the pathophysiology of many diseases, such as cancer, type-2 diabetes, viral diseases, cardiovascular disease, muscle disorders, male infertility, and neurological disorders, among others (Rayman 2012, Hatfield et al 2014, Roman et al 2014. Little is known about the role of Se in pathologies that affect the central nervous system.…”

Section: Introductionmentioning

confidence: 99%

Biological functions of selenium and its potential influence on Parkinson's disease

Ellwanger

Franke

Bordin

et al. 2016

An. Acad. Bras. Ciênc.

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Parkinson's disease is characterized by the death of dopaminergic neurons, mainly in the substantia nigra, and causes serious locomotor dysfunctions. It is likely that the oxidative damage to cellular biomolecules is among the leading causes of neurodegeneration that occurs in the disease. Selenium is an essential mineral for proper functioning of the brain, and mainly due to its antioxidant activity, it is possible to exert a special role in the prevention and in the nutritional management of Parkinson's disease. Currently, few researchers have investigated the effects of selenium on Parkinson´s disease. However, it is known that very high or very low body levels of selenium can (possibly) contribute to the pathogenesis of Parkinson's disease, because this imbalance results in increased levels of oxidative stress. Therefore, the aim of this work is to review and discuss studies that have addressed these topics and to finally associate the information obtained from them so that these data and associations serve as input to new research.

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Selenium and selenocysteine: roles in cancer, health, and development

Cited by 574 publications

References 89 publications

Redox active motifs in selenoproteins

Redox active motifs in selenoproteins

The role of selenium in thyroid gland pathophysiology

Biological functions of selenium and its potential influence on Parkinson's disease

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