the proportion of Se in Se-containing proteins is usually related to the relative proportions of methionine and selenomethionine. Although higher plants appear not to need Se, Se enters the food chain through plants; Se exists primarily as selenomethionine and, to a lesser extent, as selenocysteine and other sulfur amino acid analogues. Selenium concentrations in plants depend on the plant species and available Se concentrations in soil, and vary widely from deficient to toxic for animals that consume them.

After absorption by animals, selenomethionine appears not to be recognized specifically as a Se compound and is metabolized in the methionine pool. When catabolized, the released Se enters regulated Se metabolism and can be incorporated into selenocysteine in selenoproteins, into Se-transport compounds of unidentified composition, or into methylated Se excretory metabolites. Selenocysteine and inorganic Se absorbed by animals also enter regulated Se metabolic pathways. Selenocysteine is degraded to selenide by selenocysteine ß-lyase, whereas inorganic Se is reduced to selenide by glutathione. Selenide can enter anabolic pathways by conversion to selenophosphate or can be methylated and excreted (Burk and Levander, 1999).

Eleven selenoproteins have been identified in animals; the functions of several of them are still unknown, and apparently other selenoproteins exist. The four glutathione peroxidase selenoproteins that have been characterized use reducing equivalents from glutathione to catabolize hydroperoxides. Thus, they have been generally considered to protect cells from oxidative damage. However, their different locations and substrate specificities suggest that they can also be involved in metabolic regulation (Burk and Levander, 1999). Vitamin E functions in the protection of injury from hydroperoxides; consequently, there is an interaction between dietary needs for vitamin E and Se. Nevertheless, there is a dietary requirement for Se even if sufficient vitamin E is present (McDowell, 1992).

Selenium is involved in the metabolism of thyroid hormones, and combined deficiencies of iodine and Se are more severe than a deficiency of iodine alone (Levander and Burk, 1996). Iodothyronine deiodinases are selenoproteins that catalyze the deiodination of thyroxine, triiodothyronine, and reverse triiodothyronine and thus regulate the concentration of the active hormone triiodothyronine.

Thioredoxin reductase is an NADPH-dependent selenoprotein containing selenocysteine and regenerates ascorbic acid from dehydroascorbic acid in animals (May et al., 1997).

Selenoprotein P is an extracellular protein found in plasma and associated with endothelial cells. Its specific function has not been identified, but it accounts for about 45% of plasma Se in North American humans (Hill et al., 1996). Its concentration declines in Se deficiency, can be used for assessing Se status, and appears to be associated with oxidant defense.

Selenoprotein W has been found in muscle and a number of other tissues, and its concentration declines in Se deficiency (Vendeland et al., 1993). Its biochemical function is unknown, but the binding of one form to glutathione suggests that it can undergo redox changes.

Two selenophosphate synthetases that appear to be involved in Se homeostasis have been identified in animals (Guimaraes et al., 1996).

The Se in natural ingredients can be highly variable in quantity and in bioavailability (Henry and Ammerman, 1995; Levander and Burk, 1996). Se is usually added to commercial feeds in the form of sodium selenite.

Adult squirrel monkeys (Saimiri sciureus) appear to be more sensitive than rhesus monkeys to Se deficiency. Squirrel monkeys fed a semipurified torula-yeast diet with adequate vitamin E but without added Se showed weight loss, listlessness, alopecia, myopathy, and hepatic degeneration. The signs did not appear until the deficient diet was fed for 6-9 months. The signs were reversed by a single injection of 0.04 mg of Se from sodium selenite, and the animals were maintained by three injections of 0.04 mg at 2-week intervals followed by monthly injections. Untreated monkeys became moribund and died (Muth et al., 1971).

Pregnant rhesus (Macaca mulatta) monkeys were fed a semipurified diet containing Se at 0.03 or 0.2 mg·kg-1.No deficiency signs were seen in the mothers fed the Se-deficient diets for about 4 years. The young of the females fed the low-Se diets for about 2 years exhibited no deficiency signs. Although several animals fed the deficient diets died, no pathologic lesions characteristic of Se deficiency were seen. Hair analyses demonstrated that the animals fed the low-Se diet did indeed have low tissue concentrations. Plasma and erythrocyte glutathione peroxidase activities decreased in animals fed the diet low in Se and increased in animals fed the diet supplemented with Se. Cardiomyopathy, characteristic of Se deficiency, was found in a mother and infant fed a protein-deficient low-Se diet. That suggested that simultaneous deficiencies of protein and Se are required for signs of Se deficiency to be manifested (Butler et al., 1988).

Blood Se concentrations and glutathione peroxidase activities were compared in a number of species, including nonhuman primates (Butler et al., 1982; Beilsten and Whanger, 1983; Beilsten et al., 1984; Butler et al., 1988). A much greater portion of the Se was associated with glutathione peroxidase in erythrocytes of squirrel monkeys, rats, and sheep than of rhesus monkeys and humans.

The toxicity of L-selenomethionine was studied in 20 female Macaca fascicularis by administering various daily doses via a nasogastric tube (Cukierski et al., 1989). The researchers concluded that the maximal dose tolerated for 30 days was 150 g·BWkg-1·d-1 on the basis of mean body weight loss, hypothermia, dermatitis, xerosis, cheilitis, dis-



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement