Hostname: page-component-8448b6f56d-c4f8m Total loading time: 0 Render date: 2024-04-15T10:46:26.178Z Has data issue: false hasContentIssue false

Selenium, selenoproteins and human health: a review

Published online by Cambridge University Press:  27 September 2007

KM Brown*
Affiliation:
University of Aberdeen, Scotland
JR Arthur
Affiliation:
Rowett Research Institute, Aberdeen
*
*Corresponding author: Email k.m.brown@abdn.ac.uk
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Selenium is of fundamental importance to human health. It is an essential component of several major metabolic pathways, including thyroid hormone metabolism, antioxidant defence systems, and immune function. The decline in blood selenium concentration in the UK and other European Union countries has therefore several potential public health implications, particularly in relation to the chronic disease prevalence of the Western world such as cancer and cardiovascular disease. Ten years have elapsed since recommended dietary intakes of selenium were introduced on the basis of blood glutathione peroxidase activity. Since then 30 new selenoproteins have been identified, of which 15 have been purified to allow characterisation of their biological function. The long term health implications in relation to declining selenium intakes have not yet been thoroughly examined, yet the implicit importance of selenium to human health is recognised universally.

Selenium is incorporated as selenocysteine at the active site of a wide range of selenoproteins. The four glutathione peroxidase enzymes (classical GP×1, gastrointestinal GP×2, plasma GP×3, phospholipid hydroperoxide GP×4)) which represent a major class of functionally important selenoproteins, were the first to be characterised.

Thioredoxin reductase (TR) is a recently identified seleno-cysteine containing enzyme which catalyzes the NADPH dependent reduction of thioredoxin and therefore plays a regulatory role in its metabolic activity.

Approximately 60% of Se in plasma is incorporated in selenoprotein P which contains 10 Se atoms per molecule as selenocysteine, and may serve as a transport protein for Se. However, selenoprotein-P is also expressed in many tissues which suggests that although it may facilitate whole body Se distribution, this may not be its sole function.

A second major class of selenoproteins are the iodothyronine deiodinase enzymes which catalyse the 5′5-mono-deiodination of the prohormone thyroxine (T4) to the active thyroid hormone 3,3′5-triiodothyronine (T3).

Sperm capsule selenoprotein is localised in the mid-peice portion of spermatozoa where it stabilises the integrity of the sperm flagella.

Se intake effects tissue concentrations of selenoprotein W which is reported to be necessary for muscle metabolism.

It is of great concern that the health implications of the decline in Se status in the UK over the past two decades have not been systematically investigated. It is well recognised that dietary selenium is important for a healthy immune response. There is also evidence that Se has a protective effect against some forms of cancer; that it may enhance male fertility; decrease cardiovascular disease mortality, and regulate the inflammatory mediators in asthma. The potential influence of Se on these chronic diseases within the European population are important considerations when assessing Se requirement.

Type
Research Article
Copyright
Copyright © CABI Publishing 2001

References

1Schwartz, K, Foltz, SM. Se as an integral part of factor 3 against necrotic liver degeneration. J. Mountain Chemical Society 1957; 79: 3292–3.CrossRefGoogle Scholar
2Combs, SB, Combs, GF. The role of selenium in Nutrition. New York: Academic Press Inc, 1986.Google Scholar
3Arthur, JR, Brown, KM, Fairweather-Tait, SJ, Crews, HM. Dietary selenium: why do we need it and how much is enough? Nutrition & Food Science 1997; 6: 225–8.CrossRefGoogle Scholar
4Burk, RF, Hill, KE. Regulation of Selenoproteins. Annual Review of Nutrition 1993; 13: 6581.CrossRefGoogle ScholarPubMed
5Evenson, JK, Sunde, RA. Selenium incorporation into selenoproteins in the Se-adequate and Se-deficient rat. Proceedings of Society for Experimental Biology and Medicine 1988; 187: 169–80.CrossRefGoogle ScholarPubMed
6Rotruck, JT, Pope, AL, Ganther, HE, Swanson, AB, Hafeman, DG, Hoekstra, WG. Selenium: biochemical role as a component of glutathione peroxidase. Science 1973; 179: 588–90.CrossRefGoogle ScholarPubMed
7Burk, RF. Molecular biology of selenium with implications for its metabolism. FASEB 1991; 55: 2279.Google Scholar
8Chu, FF, Doroshow, JH, Esworthy, RS. Expression, characterization and tissue distribution of a new cellular selenium dependent GSHPx. J. Biol. Chem. 1993; 268: 2571–6.CrossRefGoogle ScholarPubMed
9Ursini, F, Maiorino, M, Gregolin, C.The selenoenzyme phospholipid hydroperoxide glutathione peroxidase. Biochim. Biophys. Acta. 1985; 839: 6270.CrossRefGoogle ScholarPubMed
10Bermano, G, Nicol, F, Dyer, JA, Sunde, RA, Beckett, GJ, Arthur, JR, Hesketh, JE. Tissue-specific regulation of selenoenzyme gene expression during selenium deficiency in rats. Biochem. J. 1995; 311: 425–30.CrossRefGoogle ScholarPubMed
11Weitzel, F, Ursini, F, Wendel, A.Phospholipid Hydroperoxide Glutathione Peroxidase in Various Mouse Organs During Selenium Deficiency and Repletion. Biochimica-et-Biophysica-Acta. 1990; 1036: 8894.CrossRefGoogle ScholarPubMed
12Calvin, HI, Grosshans, K, Musicant-Shikora, SR, Turner, SI. A developmental study of rat sperm and testis selenoproteins. J. Reprod. Fertil. 1987; 81: 111.CrossRefGoogle ScholarPubMed
13Avissar, N, Ornt, DB, Yagil, Y, Horowitz, S, Watkins, RH, Kerl, EA, Takahashi, K, Palmer, IS, Cohen, HJ. Human Kidney Proximal Tubules Are the Main Source of Plasma Glutathione Peroxidase. Am. J. Physiol. 1994; 266: C367–75.CrossRefGoogle ScholarPubMed
14Holmgren, A.Thioredoxin and glutaredoxin systems. J. Biol. Chem. 1989; 264: 13963–6.CrossRefGoogle ScholarPubMed
15Sun, Q-A, Wu, Y, Zappacosta, F, Jeang, KT, Lee, BJ, Hatfield, DL, Gladyshev, VN. Redox Regulation of Cell Signaling by Selenocysteine in Mammalian Thioredoxin Reductases. J. Biol. Chem. 1999; 274: 24522–30.CrossRefGoogle ScholarPubMed
16Holmgren, A.Thioredoxin and thrioredoxin reductase. Methods Enzymol. 1995; 252: 199208.CrossRefGoogle ScholarPubMed
17Mostenbocker, MA, Tappel, AL. A selenocysteine containing seleniujm transport protein in rat plasma. Biochim. Biophys. Acta. 1982; 719: 147–53.CrossRefGoogle Scholar
18Burk, RF, Hill, KE. Selenoprotein P: A selenium rich extra cellular glycoprotein. J. Nutr. 1994; 124(10): 1891–7.CrossRefGoogle Scholar
19Arthur, JR, Nicol, F, Becket, GT. Selenium deficiency, thyroid hormone metabolism and thyroid hormone deiodinases. Am. J. Clin. Nutr. 1993; s57: 5236–9.Google Scholar
20Olivieri, O, Girrelli, D, Azzini, M.Low selenium status in the elderly influences thyroid hormones. Clin. Sci. 1995; 89: 637–42.CrossRefGoogle ScholarPubMed
21Ursini, F, Heim, S, Kiess, M, Maiorino, M, Roveri, A, Wissing, J, Flohe, L.Dual function of the selenoprotein PHGPx during sperm maturation. Science 1999; 285: 1393–6.CrossRefGoogle ScholarPubMed
22Venzina, D, Mauffette, F, Roberts, KD. selenium vitamin E supplementation in infertile men. Biol. Trace Elem. Res. 1996; 53: 6583.CrossRefGoogle Scholar
23Yeh, JY, Vendeland, SC, Gu, QP. Dietary selenium increases selenoprotein W levels in rat tissues. J. Nutr. 1997; 127: 2165–72.CrossRefGoogle ScholarPubMed
24Westermarck, HW. Selenium in long term feeding and the frequency of white muscle disease in cattle in Finland during the years 1978–1985. Journal of Agricultural Science Finland 1987; 59: 4750.Google Scholar
25Ishihara, H, Kanda, F, Matsushita, T, et al. White muscle disease in humans: myopathy caused by selenium deficiency in anorexia nervosa under long term total parenteral nutrition. J. Neurol. Neurosur PS 1999; 67: 829–30.CrossRefGoogle ScholarPubMed
26Casey, CE, Guthrie, BE, Friend, GM. Selenium in human tissues from New Zealand. Arch. Environ. Health 1982; 37: 133–5.CrossRefGoogle ScholarPubMed
27Thorling, EB, Overvad, K, Heerfordt, A.Serum selenium in Danish blood bank donors. Biol. Trace Elem. Res. 1985; 8: 6573.CrossRefGoogle ScholarPubMed
28Alfthan, G, Neve, J.Reference values for serum selenium in various areas – Evaluated according to the TRACY protocol. Journal Trace Elements in Medicine and Biology 1996; 10: 7787.CrossRefGoogle Scholar
29Levander, OA. Scientific rationale for the 1989 recommended dietary allowance for selenium. Journal of American Dietetic Association 1991; 91: 1572–6.CrossRefGoogle ScholarPubMed
30WHO Food and Agriculture Organisation, International Atomic Energy Agency expert group. Trace elements in human nutrition and health. Geneva: WHO, 1996.Google Scholar
31Levander, O, Whanger, P.Deliberations and Evaluations of the Approaches, Endpoints and Paradigns for Selenium and Iodine Dietary Recommendations. J. Nutr. 1996; 126: 2427s–34s.CrossRefGoogle ScholarPubMed
32Molnar, J, MacPherson, A, Barclay, I, Molnar, P.Selenium content of convenience and fast foods in Ayrshire, Scotland International. Journal Food Sciences and Nutrition 1995; 46: 343–52.Google Scholar
33Shortt, CT, Duthie, GG, Robertson, JD, Morrice, PC, Nicol, F, Arthur, JR. Selenium studies of a group of Scottish adults. Eur. J. Clin. Nutr. 1997; 51: 15.CrossRefGoogle ScholarPubMed
34MAFF Joint Food Safety and Standards Group. Food Surveillance Information Sheet 1997 No 127.Google Scholar
35Brown, KM, Pickard, K, Nicol, F, Duthie, G, Beckett, G, Arthur, JR. Effects of organic and inorganic selenium supplementation on selenoenzyme activity in blood lymphocytes, granulocytes, platelets and erythrocytes. Clin. Sci. 2000; 98: 593–9.CrossRefGoogle ScholarPubMed
36Diplock, AT. Indexes of Selenium Status in Human Populations American. J. Clin. Nutr. 1993; 57: S256–8.CrossRefGoogle Scholar
37Rayman, MP. Dietary selenium: Time to act – Low bioavailability in Britain and Europe could be contributing to cancers, cardiovascular disease, and subfertility. Br. Med. J. 1997; 314: 387–8.CrossRefGoogle Scholar
38Roveri, A, Maiorino, M, Ursini, F.Enzymatic and immunological measurements of soluble and membrane- bound phospholipid-hydroperoxide glutathione peroxidase. Methods Enzymol. 1994; 233: 202–12.CrossRefGoogle ScholarPubMed
39Taylor, EW. Selenium and cellular immunity – Evidence that selenoproteins may be encoded in the +1 reading frame overlapping the human CD4, CD8, and HLA-DR genes. Biol. Trace Elem. Res. 1995; 49: 8595.CrossRefGoogle ScholarPubMed
40Kiremidjian-Schumacher, L, Roy, M, Wishe, HI, Cohen, MW, Strotzky, G.Supplementation with selenium and human immune cell functions. 2. Effect on cytotoxic lymphocytes and natural killer cells. Biol. Trace Elem. Res. 1994; 41: 115–27.CrossRefGoogle ScholarPubMed
41Roy, M, Kiremidjian-Schumacher, L, Wishe, H, Cohen, MW, Stotzy, G.Supplementation with selenium and human immune cell functions 1. Effect on lymphocyte proliferation and interleukin 2 receptor expression. Biol. Trace Elem. Res. 1994; 41: 103–14.CrossRefGoogle ScholarPubMed
42Clark, LC, Combs, GF, Turnbull, BW, Slate, EH, Chalker, DK, Chow, J, Davis, LS, Glover, RA, Graham, GF, Gross, EG, Krongrad, A, Lesher, JL, Park, HK, Sanders, BB, Smith, CL, Taylor, JR. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: A randomized controlled trial. J. Am. Med. Assoc. 1996; 276: 1957–63.CrossRefGoogle ScholarPubMed
43Gladyshev, VN, Jeang, KT, Stadtman, TC. Selenocysteine, identified as the penultimate C-terminal residue in human T-cell thioredoxin reductase, corresponds to TGA in the human placental gene. Proc. Natl. Acad. Sci. U.S.A. 1996; 93: 6146–51.CrossRefGoogle ScholarPubMed
44Weitzel, F, Wendel, A.Selenoenzymes Regulate the Activity of Leukocyte 5-Lipoxygenase via the Peroxide Tone. J. Biol. Chem. 1993; 268: 6288–92.CrossRefGoogle ScholarPubMed
45Steinhilber, D, Herrmann, T, Rothe, HJ. Selenium dependent peroxidases suppress 5-lypoxygenase activity in B-lymphocytes and immature myeloid cells. Eur. J. Biochem. 1996; 242: 90–7.Google Scholar
46Infante, JP. Vitamin E and selenium participation in fatty acid desaturation: A proposal for an enzymatic function of these nutrients. Mol. Cell Biochem. 1986; 69(2): 93108.CrossRefGoogle ScholarPubMed
47Seaton, A, Godden, DJ, Brown, K.Increase in asthma: A more toxic environment or a more susceptible population. Thorax 1994; 49: 171–4.CrossRefGoogle ScholarPubMed
48Arthur, JR. Functional indicators of iodine and selenium status. Proceedings of the Nutrition Society 1999; 58: 507–12.Google ScholarPubMed