Abstract
We now know much about selenium (Se) incorporation into selenoproteins, and there is considerable interest in the optimum form of Se for supplementation and prevention of cancer. To study the flux of 75Se into selenoprotein, rats were fed 0 to 5 μg Se/g diet as selenite for 50–80 d and injected iv with 50 μCi of 75Se-labeled selenite, selenate, selenodiglutathione, selenomethionine, or selenobetaine at tracer levels (~0.5 μg Se). The rats were killed at various times and 75Se incorporation into selenoproteins was assessed by SDS/PAGE. These studies found that there is very rapid Se metabolism from this diverse set of selenocompounds to the common intermediate used for synthesis and incorporation of 75Se into the major selenoproteins in a variety of tissues. No selenocompound was uniquely or preferentially metabolized to provide Se for selenoprotein incorporation. Examination of the SDS/PAGE selenoprotein profiles, however, reveals that synthesis of selenoproteins is only part of the full Se metabolism story. The 75Se missing from the selenoprotein profiles, especially at early timepoints, is likely to be both low-MW and high-MW selenosugars and related precursors, as we recently found in livers of turkeys fed Se-adequate and high-Se diets. Differential metabolism of different selenocompounds into different selenosugar species may occur; these species may be involved in prevention of cancer or other diseases linked to Se status and may be associated with Se toxicity. Additional studies using HPLC-mass spectroscopy will likely be needed to fully flesh out the complete metabolism of selenium.
Highlights
We know much about selenium (Se) incorporation into selenoproteins
Using HPLC coupled with Se-specific and molecule-specific mass spectroscopy, we recently found these low-molecular weight (MW) species in livers of turkeys fed Se-adequate and high-Se diets, but we found high-MW selenosugar species linked via selenodisulfide bonds (Se-S) to protein
The overall result is a clear pattern of very rapid Se metabolism from a diverse set of selenocompounds to a common intermediate used for synthesis and incorporation into well-defined 75Se selenoprotein patterns for at least the major selenoproteins: plasma selenoprotein P (SELENOP) and GPX3, liver and heart GPX1 and the 65 kDa species, and testes GPX4
Summary
We know much about selenium (Se) incorporation into selenoproteins. Se at the selenide level is metabolized to selenophosphate, esterified to serine while attached to a novel selenocysteine tRNA, and incorporated into the selenoprotein backbone during translation at the position specified by a UGA codon and requiring a 3’UTR stem-loop selenocysteine (Sec) insertion sequence [1,2,3,4,5,6]. Cloning and expression of UGA-containing transcripts has demonstrated that the mammalian selenoproteome consists of 24–25 selenoproteins [8, 9]. When these studies were conducted there was considerable interest in the optimum form of Se for supplementation and prevention of cancer [10,11,12]. Both inorganic Se, like selenite, and organic Se, like selenomethionine (SeMet), had been shown to readily provide Se for GPX synthesis [13] and to prevent cancer in animal models [14]. Se was known to be toxic at higher levels [21,22,23], but it was not clear if there were additional selenoproteins that appear only under high Se status or that are associated just with Se toxicity [24, 25]
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