Selenomethionine toxicity

Although it is toxic in large doses, selenium is an essential micronutrient in all known forms of life. It is a component of the unusual amino acids selenocys-teine and selenomethionine. In humans, selenium is a trace element nutrient. 

Membrane-integrated proteins were always hard to express in cell-based systems in sufficient quantity for structural analysis. In cell-free systems, they can be produced on a milligrams per milliliter scale, which, combined with labeling with stable isotopes, is also very amenable forNMR spectroscopy [157-161]. Possible applications of in vitro expression systems also include incorporation of selenomethionine (Se-Met) into proteins for multiwavelength anomalous diffraction phasing of protein crystal structures [162], Se-Met-containing proteins are usually toxic for cellular systems [163]. Consequently, rational design of more efficient biocatalysts is facilitated by quick access to structural information about the enzyme. 

A thiolase (Eq. 13-35) from Clostridium kluyveri is one of only two known selenoproteins that contain selenomethionine.569 However, the selenomethionine is incorporated randomly in place of methionine. This occurs in all proteins of all organisms to some extent and the toxicity of selenium may result in part from excessive incorporation of selenomethionine into various proteins. 

It is well known that the toxicity of many elements depends on the physicochemical forms they assume. So, for instance, determining the total content of a certain element in a sample is definitely not sufficient to measure its toxicity. Selenium is a case in point in small amounts this element is essential to human health. But the transition from the necessary amount (about 70pg of selenium per day for an adult) to a toxic dose (about 800 pg of selenium per day) is relatively easy. In rats, moreover, the fatal dose of Se(IV) compounds is 3.2 mg kg 1 of body mass, whereas for dimethyl selenide it is 1600 mg kg 1 of body mass. Nonorganic selenium compounds [Se(IV) and Se(VI)] are believed to be the most toxic ones, whereas in the environment selenium occurs most commonly bound to amino acids (selenomethionine and selenocysteine). The least toxic forms seem to be the volatile methyl compounds of selenium, which are metabolites of a detoxication process. 

Alaejos, M.S. and Romero, C.D. 1995. Selenium in human lactation. Nutr. Rev. 53, 159-166. Ammar, E.M. and Couri, D. 1981. Acute toxicity of sodium selenite and selenomethionine in mice after ICV or IV administration. Neurotoxicology 2, 383-386. 

Cukierski, M.J., Willhite, C.C., Lasley, B.L., Hendrie, T.A., Book, S.A., Cox, D.N., and Hendricks, A.G. 1989. 30-day oral toxicity study of L-selenomethionine in female long-tailed macaques (Macaca fascicularis). Fundam. Appl. Toxicol. 13, 26—39. 

Eustice, D.C., Krull, F.J., and Shrift, A. 1981. Selenium toxicity aminoacylation and peptide bond formation with selenomethionine. Plant Physiol. 67, 1054-1058. 

Heinz, G.H., Hoffman, D.J., and LeCaptain, L.J. 1996. Toxicity of seleno-L-methionine, seleno-D,L-selenomethionine, high selenium wheat, and selenized wheat to mallard ducklings. Arch. Environ. Contam. Toxicol. 31(1), 93-99. 

McAdam, P.A. and Levander, O.A. 1987. Chronic toxicity of dietary selenium fed to rats as D- or L-selenomethionine, selenite or selenate. Nutr. Res. 7, 601-610. 

McAdam, P.A., Wood, L.E., and Levander, O.A. 1985. Comparative acute toxicity and nutritional biopotency of injected doses of D- versus L-selenomethionine (SeMet) in rats. Am. J. Clin. Nutr. 41, 864. 

Schrauzer, G.N. 2000. Selenomethionine a review of its nutritional significance, metabolism and toxicity. J. Nutr. 130, 1653-1656. 

Salbe, A. D., and Levander, O. A. (1990). Comparative toxicity and tissue retention of selenium in methionine-deficient rats fed sodium selenate or L-selenomethionine. /. Nutr. 120, 207-212. 

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