{"title":"Selenium in biology.","authors":"D V Frost, P M Lish","doi":"10.1146/annurev.pa.15.040175.001355","DOIUrl":null,"url":null,"abstract":"<p><p>The role of Se in biology appears from the evidence now at hand to be as a catalyst par excellence. As unique prosthetic group of a variety of enzymes, presumably as Se(2-), Se functions with tocopherol to protect cell and organelle membranes from oxidative damage, to facilitate the union between oxygen and hydrogen at the end of the metabolic chain, and to transfer ions across cell membranes, in protein synthesis in erythrocytes and in liver organelles, in immunoglobulin synthesis, and in ubiquinone syntheses. As perhaps the most versatile and rapid nucleophile, Se is thought to amplify and orient SH in equilibrium -S-S-interactions involving glutathione and proteins. Its toxicity appears to be due to overaccumulation of selenite ions, which act as oxidants to inhibit SH interactions. Such toxicity is readily avoided or reversed in many ways. Although not yet recognized as essential for man, Se is clearly essential for many animal species and some microorganisms. As the active selenide, Se emerged as the target for many heavy metal toxicities; contrariwise, as a specific antidote against heavy metal toxicities. Despite all this, its unusual toxicity and the many preconceived notions about Se continue to confuse attitudes toward the safe uses of selenicals. From a suspected cause of cancer, Se metamorphosed, via evidence over many years, into something of possible anticancer value. Interrelations between Se, Vitamin E, the ubiquinones, and various chronic diseases appear as beckoning research areas. The reported veterinary values of Se-tocopherol combinations in animals, together with clinical evidence, plus human and animal evidence for safety, offer promise for intensive medical investigation. The historical confusion and misunderstandings regarding Se must be corrected, however, before advantage can be taken of its potential for human welfare. The many misjudgments about Se, ever since 1900 and more obviously since the 1930s, have involved other trace elements. Unrealistic regulations stemming from these misunderstandings prevail worldwide. Evidence suggests that, once the nutrition biochemistry and toxicology of Se is sufficiently understood and appreciated, major breakthroughs in agriculture, medicine, and public health can result. Much has been accomplished along these lines in New Zealand in animal agriculture, in the US and other countries in veterinary medicine, and in Mexico in human medicine.</p>","PeriodicalId":75521,"journal":{"name":"Annual review of pharmacology","volume":"15 ","pages":"259-84"},"PeriodicalIF":0.0000,"publicationDate":"1975-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev.pa.15.040175.001355","citationCount":"178","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1146/annurev.pa.15.040175.001355","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 178
Abstract
The role of Se in biology appears from the evidence now at hand to be as a catalyst par excellence. As unique prosthetic group of a variety of enzymes, presumably as Se(2-), Se functions with tocopherol to protect cell and organelle membranes from oxidative damage, to facilitate the union between oxygen and hydrogen at the end of the metabolic chain, and to transfer ions across cell membranes, in protein synthesis in erythrocytes and in liver organelles, in immunoglobulin synthesis, and in ubiquinone syntheses. As perhaps the most versatile and rapid nucleophile, Se is thought to amplify and orient SH in equilibrium -S-S-interactions involving glutathione and proteins. Its toxicity appears to be due to overaccumulation of selenite ions, which act as oxidants to inhibit SH interactions. Such toxicity is readily avoided or reversed in many ways. Although not yet recognized as essential for man, Se is clearly essential for many animal species and some microorganisms. As the active selenide, Se emerged as the target for many heavy metal toxicities; contrariwise, as a specific antidote against heavy metal toxicities. Despite all this, its unusual toxicity and the many preconceived notions about Se continue to confuse attitudes toward the safe uses of selenicals. From a suspected cause of cancer, Se metamorphosed, via evidence over many years, into something of possible anticancer value. Interrelations between Se, Vitamin E, the ubiquinones, and various chronic diseases appear as beckoning research areas. The reported veterinary values of Se-tocopherol combinations in animals, together with clinical evidence, plus human and animal evidence for safety, offer promise for intensive medical investigation. The historical confusion and misunderstandings regarding Se must be corrected, however, before advantage can be taken of its potential for human welfare. The many misjudgments about Se, ever since 1900 and more obviously since the 1930s, have involved other trace elements. Unrealistic regulations stemming from these misunderstandings prevail worldwide. Evidence suggests that, once the nutrition biochemistry and toxicology of Se is sufficiently understood and appreciated, major breakthroughs in agriculture, medicine, and public health can result. Much has been accomplished along these lines in New Zealand in animal agriculture, in the US and other countries in veterinary medicine, and in Mexico in human medicine.
从目前掌握的证据来看,硒在生物学中的作用似乎是一种卓越的催化剂。Se是多种酶的独特假基,可能是Se(2-),它与生育酚一起起保护细胞和细胞器膜免受氧化损伤的作用,促进代谢链末端氧和氢的结合,并在细胞膜上转移离子,参与红细胞和肝细胞器的蛋白质合成,免疫球蛋白的合成和泛醌的合成。Se可能是最通用和最快速的亲核试剂,被认为可以放大和定向SH在平衡- s - s -相互作用中涉及谷胱甘肽和蛋白质。其毒性似乎是由于亚硒酸盐离子的过度积累,亚硒酸盐离子作为氧化剂抑制SH相互作用。这种毒性可以很容易地通过许多方法避免或逆转。虽然硒尚未被认为是人类所必需的,但它显然是许多动物物种和一些微生物所必需的。硒作为一种活性硒化物,成为许多重金属毒性的靶点;相反,作为重金属中毒的特殊解毒剂。尽管如此,硒的不同寻常的毒性和对硒的许多先入为主的观念仍然使人们对硒类药物安全使用的态度变得混乱。多年来的证据表明,硒从一种被怀疑致癌的物质转变为可能具有抗癌价值的物质。硒、维生素E、泛醌和各种慢性疾病之间的相互关系成为诱人的研究领域。据报道,硒-生育酚组合物在动物中的兽医价值,加上临床证据,以及人类和动物的安全性证据,为深入的医学调查提供了希望。然而,必须纠正历史上对Se的混淆和误解,才能利用Se对人类福祉的潜力。自1900年以来,对硒元素的许多错误判断,以及自20世纪30年代以来更为明显的错误判断,都涉及到其他微量元素。由于这些误解而产生的不切实际的规定在世界范围内普遍存在。有证据表明,一旦硒的营养生物化学和毒理学得到充分理解和重视,就可以在农业、医学和公共卫生方面取得重大突破。在新西兰的畜牧业、美国和其他国家的兽医学以及墨西哥的人类医学方面,沿着这条路线取得了很大成就。