Journal
ANNUAL REVIEW OF NUTRITION, VOL 35
Volume 35, Issue -, Pages 109-134Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-nutr-071714-034250
Keywords
selenoprotein hierarchy; selenoprotein P; apolipoprotein E receptor-2; megalin; selenocysteine lyase; human selenium metabolism
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Funding
- NIH [ES02497, DK58763]
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Selenium is regulated in the body to maintain vital selenoproteins and to avoid toxicity. When selenium is limiting, cells utilize it to synthesize the selenoproteins most important to them, creating a selenoprotein hierarchy in the cell. The liver is the central organ for selenium regulation and produces excretory selenium forms to regulate whole-body selenium. It responds to selenium deficiency by curtailing excretion and secreting selenoprotein P (Sepp1) into the plasma at the expense of its intracellular selenoproteins. Plasma Sepp1 is distributed to tissues in relation to their expression of the Sepp1 receptor apolipoprotein E receptor-2, creating a tissue selenium hierarchy. N-terminal Sepp1 forms are taken up in the renal proximal tubule by another receptor, megalin. Thus, the regulated whole-body pool of selenium is shifted to needy cells and then to vital selenoproteins in them to supply selenium where it is needed, creating a whole-body selenoprotein hierarchy.
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