SELENIUM METABOLISM AND GLUTATHIONE PEROXIDASE SYNTHESIS

该项目建议研究导致硒(Se)代谢的 谷胱甘肽过氧化物酶(GSH-Px)掺入Se。GSH-PX是唯一 已知的硒酶存在于动物体内，而硒存在于该酶中 作为一种氨基酸，硒半胱氨酸(Se-Cys)被结合到多肽中 酶的主干。这种含Se元素的形成机理 部分是未知的。我的初步结果表明，Se-Cys 部分是由无机形式的Se共价结合形成的 一种氨基酸残基，可能是丝氨酸，已经存在于多肽中 酶的主干。植物性食品中硒的主要形态 来源被认为是硒蛋氨酸(Se-Met)，但 膳食Se-Met用于合成GSH-Px的形式尚未被 特色化的。此外，我们已经证明，饮食水平 蛋氨酸对Se-Met中Se的利用率有显著影响 对于GSH-PX的合成，可能是因为Se-Met可以被结合到 蛋白质作为蛋氨酸类似物。因此，各种无机物和 Se合成GSH-Px的有机形态取决于Se的性质 体内的新陈代谢。 为了加深我们对硒代谢的理解，我们打算继续 以下是具体目标：1)查明 GSH-Px中Se-Cys部分的碳骨架及其鉴定 Se-Cys部分的形成机制；2)抗GSH-Px的利用 确定Se在GSH-Px蛋白调节中作用的抗体 3)利用灌流的大鼠肝脏进一步鉴定 多种含硒代谢产物为GSH-Px提供硒的能力 合成；4)Se-Met-Se-Met掺入两种命运的比较 转化为一般身体蛋白质与Se-Met降解释放Se GSH-PX合成--测定食物中硒的生物利用率 “加硒酵母”。 这项研究的总体目标是更好地理解 Se的代谢和随后合成GSH-Px的有效性。 这一知识之所以重要，是因为硒的广泛使用 在动物营养方面的补充，而且由于不断增加的 人类补充硒的倾向。

This project proposes to examine the metabolism of selenium (Se) leading to Se incorporation into glutathione peroxidase (GSH-Px). GSH-Px is the only known selenoenzyme present in animals, and the Se is present in the enzyme as an amino acid, selenocysteine (Se-Cys), incorporated into the peptide backbone of the enzyme. The mechanism for formation of this Se-containing moiety is unknown. My initial results have indicated that the Se-Cys moiety is formed by the covalent attachment of an inorganic form of Se to an amino acid residue, perhaps serine, already present in the peptide backbone of the enzyme. The major form of the Se in foodstuffs of plant origin is thought to be selenomethionine (Se-Met), but the metabolism of dietary Se-Met to the form used for GSH-Px synthesis has not been characterized. Furthermore, we have shown that the level of dietary methionine can have a dramatic effect on the availability of Se from Se-Met for GSH-Px synthesis, perhaps because Se-Met can be incorporated into protein as a Met analog. Thus the availability of various inorganic and organic forms of Se for GSH-Px synthesis depends on the nature of Se metabolism in the body. To further our understanding of Se metabolism, we intend to pursue the following specific objectives: 1) identification of the origin of the carbon skeleton of the Se-Cys moiety in GSH-Px and thus identification of the mechanism used to form the Se-Cys moiety; 2) utilization of anti-GSH-Px antibodies to determine the role of Se in the regulation of GSH-Px protein synthesis; 3) utilization of the perfused rat liver to further characterize the ability of various Se-containing metabolites to provide Se for GSH-Px synthesis; 4) comparison of the two fates of Se-Met -- Se-Met incorporation into general body proteins versus Se-Met degradation to release Se for GSH-Px synthesis -- to determine Se bioavailability in foods and in "selenized yeast". The overall objective of this research is to better understand Se metabolism and the subsequent availability of Se for GSH-Px synthesis. This knowledge is important because of the widespread use of Se supplementation in animal nutrition, and because of the increasing inclination of humans to supplement themselves with Se.