Selenoprotein P: An Extracellular Protein with Unique Physical Characteristics and a Role in Selenium Homeostasis

• Published in: Annual review of nutrition Vol. 25; no. 1; pp. 215 - 235
• Main Authors: Burk, R.F, Hill, K.E
• Format: Journal Article
• Language: English
• Published: Palo Alto, CA Annual Reviews 01.01.2005; Annual Reviews, Inc
• Subjects: Amino Acid Sequence; Amino acids; Analytical, structural and metabolic biochemistry; Animals; antioxidant activity; Biological and medical sciences; dietary mineral supplements; dietary minerals; Dietary Supplements; Diquat; disulfide bonds; Fundamental and applied biological sciences. Psychology; glutathione peroxidase; Glycosylation; health promotion; Heparin - metabolism; Homeostasis; homocysteine; Humans; Mercury - metabolism; Miscellaneous; Molecular Sequence Data; nutrient deficiencies; nutrient transport; Nutritional status; Oxidizing agents; Peroxidation; Protein Isoforms; Proteins; Proteins - analysis; Proteins - genetics; Proteins - physiology; quantitative structure-activity relationships; redox potential; selenenylsulfide bond; Selenium; Selenium - administration & dosage; Selenium - metabolism; seleno amino acids; selenocysteine residues; Selenoprotein P; Selenoproteins; Human; Molecular form; Enzyme; Biological transport; multiple selenocysteine residues; Homeostasis; isoforms; Review; Extracellular; Vertebrata; Selenoprotein; selenenylsulfide bonds; Mammalia; selenium transport; Oxidoreductases; Selenium; Glycine dehydrogenase (decarboxylating)
• ISSN: 0199-9885; 1545-4312
• DOI: 10.1146/annurev.nutr.24.012003.132120

Selenoprotein P is an abundant extracellular glycoprotein that is rich in selenocysteine. It has two domains with respect to selenium content. The N-terminal domain of the rat protein contains one selenocysteine residue in a UxxC redox motif. This domain also has a pH-sensitive heparin-binding site and two histidine-rich amino acid stretches. The smaller C-terminal domain contains nine selenocysteine and ten cysteine residues. Four isoforms of selenoprotein P are present in rat plasma. They share the same N terminus and amino acid sequence. One isoform is full length and the three others terminate at the positions of the second, third, and seventh selenocysteine residues. Selenoprotein P turns over rapidly in rat plasma with the consequence that approximately 25% of the amount of whole-body selenium passes through it each day. Evidence supports functions of the protein in selenium homeostasis and oxidant defense. Selenoprotein P knockout mice have very low selenium concentrations in the brain, the testis, and the fetus, with severe pathophysiological consequences in each tissue. In addition, those mice waste moderate amounts of selenium in the urine. Selenoprotein P binds to endothelial cells in the rat, and plasma levels of the protein correlate with prevention of diquat-induced lipid peroxidation and hepatic endothelial cell injury. The mechanisms of these apparent functions remain speculative and much work on the mechanism of selenoprotein P function lies ahead. Measurement of selenoprotein P in human plasma has shown that it is depressed by selenium deficiency and by cirrhosis. Selenium supplementation of selenium-deficient human subjects showed that glutathione peroxidase activity was optimized before selenoprotein P concentration was optimized, indicating that plasma selenoprotein P is the better index of human selenium nutritional status.