Mechanism, Structure, and Biological Role of Selenocysteine Lyase
Selenocysteine lyase is a pyridoxal 5′-phosphate-dependent enzyme catalyzing the degradation of l -selenocysteine to l -alanine and elemental selenium. It is unique in that it acts exclusively on l -selenocysteine but not on its sulfur counterpart, l -cys
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Mechanism, Structure, and Biological Role of Selenocysteine Lyase Hisaaki Mihara, Ryuta Tobe, and Nobuyoshi Esaki
Abstract Selenocysteine lyase is a pyridoxal 5′-phosphate-dependent enzyme catalyzing the degradation of L-selenocysteine to L-alanine and elemental selenium. It is unique in that it acts exclusively on L-selenocysteine but not on its sulfur counterpart, L-cysteine. The enzyme is proposed to function not only in the recycling of selenium via degradation of L-selenocysteine derived from selenoproteins, but also in energy metabolism linked to obesity and metabolic syndrome. Crystallographic studies have shed light on the catalytic mechanism that allows the enzyme to distinguish between L-selenocysteine and L-cysteine, which possibly contributes in uncovering the physiological role of selenocysteine lyase in mammals. Keywords Catalytic mechanism • Selenium metabolism • Selenium recycling • Selenopersulfide • Selenoprotein biosynthesis
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Mammalian Selenium Metabolism
The chemical forms of selenium in diets are mostly either selenomethionine, selenocysteine, selenite or selenate. Among these, selenomethionine is the predominant form, because about 90 % of the total selenium in plants exists as protein selenomethionine residues that have randomly and frequently replaced native methionine residues [1]. Although inorganic selenium compounds are less abundant than selenomethionine, they can easily be taken up as a source of selenium for selenoprotein biosynthesis [2]. Selenate needs to be reduced to selenite prior to its utilization as a selenium source, through a mechanism similar to the nitrate reduction process. Alternatively, selenate can be reduced to selenite by adenosine 5′-phosphosulfate
H. Mihara (*) • R. Tobe Department of Biotechnology, College of Life Sciences, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan e-mail: [email protected] N. Esaki Kyoto Study Center, The Open University of Japan, Kyoto 600-8216, Japan © Springer Science+Business Media, LLC 2016 D.L. Hatfield et al. (eds.), Selenium, DOI 10.1007/978-3-319-41283-2_10
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Fig. 10.1 Selenium metabolism and incorporation of selenium into selenoproteins. ATP adenosine 5´-phosphate, APS adenosine 5´-phsphosulfate, APSe adenosine 5´-phosphoselenate, SAM S-adenosylmethionine, SCLY selenocysteine lyase
reductases similar to the reduction of sulfate to sulfite. Selenite is then reduced to selenide by glutathione or thioredoxin reductase. As shown in Fig. 10.1, selenide is the key compound for selenoprotein biosynthesis. A selenocysteine residue is encoded by the UGA codon in selenoprotein mRNA, which is decoded by selenocysteyl-tRNA[Ser]Sec [3, 4]. The selenocysteine moiety on selenocysteyl-tRNA[Ser]Sec is biosynthesized using selenophosphate, which is produced from selenide and ATP by selenophosphate synthetase [5, 6]. However, the metabolic pathway providing selenide for selenophosphate synthetase remains unclear. Excess selenide is excreted in urine as trimethylselenide or dimethylselenide after methy
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