C J Bates, MRC Human Nutrition Research,
© 2005 Elsevier Ltd. All rights reserved.
The realization that selenium (Se) may be an essential micronutrient for human diets has arisen only recently, in the second half of the twentieth century. Selenium deficiency, attributable to low soil selenium levels in farm animals, especially sheep that are afflicted by selenium-responsive 'white muscle disease,' has been recognized for at least half a century. However, the more recent identification of Keshan and Kashin-Beck diseases as endemic selenium-responsive conditions, occurring in a central 4000+-km-wide belt of central China and in areas of Russia, demonstrated conclusively that not only is selenium an essential element for man but also deficiencies occur naturally and require public health measures to alleviate them. Selenium incorporation into plants is affected by the acidity of the soil and by the concentrations of iron and aluminum present so that selenium content of human diets is modulated by these components of the environment. The very recent discovery that these diseases probably arise through the interaction of selenium deficiency with enhanced viral virulence has added a further layer of complexity, but it does not alter the fact that selenium is an essential dietary component that cannot be substituted by any other element. Another complicating factor is that moderately increased soil selenium concentrations result in the opposite condition of selenosis, or selenium overload, with equally debilitating consequences. Of all elements, selenium has a very narrow safe intake range, and unlike some other potentially toxic elements, it is absorbed efficiently by the intestine over a wide range of concentrations and across a variety of different molecular forms.
Unlike other elements, selenium can be incorporated in two distinct ways into proteins, either as a functional active center (in specific selenoproteins) via a selective incorporation mechanism that ensures selenocysteine insertion or alternatively by a nonspecific incorporation pathway, in which selenomethio-nine (or selenocysteine) can replace methionine or cysteine at random, without apparently conferring any special functional characteristics on the recipient proteins. This dichotomy of incorporation complicates the task of measuring status and requirements because the different dietary forms of selenium contribute differently to these two contrasting types of incorporation. Selenomethionine and supplementary selenium in the form of selenium-enriched yeast, in which the incorporated selenium is largely present as selenomethionine, contribute to the random incorporation pathway. This is followed by a gradual turnover of selenium to enrich the specific incorporation pathway. Inorganic selenium, in contrast, feeds directly into the specific incorporation pathway via selenide. Although inorganic selenium may relieve functional selenium deficiency more rapidly than organic selenium, the inorganic forms are potentially more toxic; therefore, selenomethionine supplementation is often preferred because it is safer.
Selenoproteins seem to have a number of functions, comprising various catalytic roles (glutathione peroxidases, thioredoxin reductases, and iodothyro-nine deiodinases), structural roles, detoxifying functions (e.g., selenoprotein P), and storage and transport activities. Many of these functions are incompletely understood, and advances in this area should help to clarify uncertainties about human requirements and the role of selenoproteins in disease, especially in multifactorial conditions such as cancers. Several controlled intervention trials involving selenium are under way, and these should provide evidence to underpin public health programs in the near future.
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