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SELENIUM METABOLISM AND GLUTATHIONE PEROXIDASE SYNTHESIS

硒代谢和谷胱甘肽过氧化物酶合成

基本信息

批准号：
3152659
负责人：
Roger A Sunde
金额：
$ 8.36万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-07-01 至 1988-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3152659
关键词：
aminoacid metabolism antibody cysteine genetic translation glutathione peroxidase high performance liquid chromatography liver metabolism messenger RNA metal metabolism metalloenzyme methionine muscle pharmacology radiotracer selenium

项目摘要

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.

该项目建议检查硒（Se）的代谢，硒掺入谷胱甘肽过氧化物酶（GSH-Px）。 GSH-Px是唯一已知的硒酶存在于动物中，并且Se存在于酶中作为氨基酸，硒代半胱氨酸（Se-Cys），掺入肽中酶的骨架。这种含硒矿物的形成机制部分未知。我的初步结果表明硒半胱氨酸部分通过无机形式的Se共价连接到肽中已经存在的氨基酸残基，可能是丝氨酸酶的骨架。植物性食品中硒的主要存在形式硒的来源被认为是硒蛋氨酸（Se-Met），但硒的代谢膳食硒蛋氨酸用于GSH-Px合成的形式还没有表征了此外，我们已经表明，饮食水平蛋氨酸可以对来自Se-Met的Se的可用性具有显著影响对于GSH-Px合成，可能是因为Se-Met可以被掺入到蛋白质作为Met类似物。因此，各种无机和用于GSH-Px合成的硒的有机形式取决于硒的性质体内的新陈代谢。为了进一步了解硒的代谢，我们打算继续研究硒的代谢。具体目标如下：1）确定 GSH-Px中Se-Cys部分的碳骨架，从而鉴定 Se-Cys的形成机制; 2）抗GSH-Px抗体的应用抗体，以确定硒在GSH-Px蛋白调节中的作用合成; 3）利用灌注的大鼠肝脏进一步表征各种含硒代谢物为GSH-Px提供硒的能力合成; 4）Se-Met两种命运的比较-- Se-Met掺入与硒蛋氨酸降解释放硒形成 GSH-Px合成--测定食品和饲料中硒的生物有效性 “硒化酵母”。本研究的总体目标是更好地了解Se 硒的代谢和随后的GSH-Px合成的可用性。由于硒的广泛使用，动物营养的补充，由于越来越多的人类倾向于补充硒。