title: Regulation of Selenium Metabolism and Transport.
abstract: 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.
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0252; email: raymond.burk@vanderbilt.edu , kristina.hill@vanderbilt.edu.
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Burk
authors.forename: Kristina E
authors.initials: KE
authors.lastname: Hill
mesh_terms: D000818:Animals; D001682:Biological Availability; D001692:Biological Transport; D015415:Biomarkers; D004032:Diet; D019587:Dietary Supplements; D006304:Health Status; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D026502:LDL-Receptor Related Proteins / Q000502:physiology; D008099:Liver / Q000502:physiology; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000502:physiology; D009751:Nutritional Requirements; D009928:Organ Specificity; D012643:Selenium / Q000172:deficiency / Q000378:metabolism* / Q000493:pharmacokinetics; D017279:Selenocysteine / Q000378:metabolism; D012645:Selenomethionine / Q000378:metabolism; D051149:Selenoprotein P / Q000032:analysis / Q000097:blood; D051140:Selenoproteins / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D015415:Biomarkers; D026502:LDL-Receptor Related Proteins; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D051149:Selenoprotein P; D051140:Selenoproteins; C098773:low density lipoprotein receptor-related protein 8; D017279:Selenocysteine; D012645:Selenomethionine; D012643:Selenium
keywords: apolipoprotein E receptor-2; human selenium metabolism; megalin; selenocysteine lyase; selenoprotein P; selenoprotein hierarchy