Flohé Leopold
Otto-von-Guericke-Universität, Universitätsplatz 2, D-39106 Magdeburg, and MOLISA GmbH, Brenneckestrasse 20, D-39118 Magdeburg, Germany.
Biochim Biophys Acta. 2009 Nov;1790(11):1389-403. doi: 10.1016/j.bbagen.2009.03.031. Epub 2009 Apr 7.
The serendipitous discoveries leading to the present knowledge on selenium's role in biology are reviewed. Detected in 1818 as by-product of sulphuric acid production, selenium first attracted medical attention as an industrial hazard. In parallel selenium intoxication was recognized as cause of life stock diseases. Reports on teratogenic effects and carcinogenicity of selenium followed since the middle of the past century. In 1954 first hints towards specific biological functions of selenium were contributed from microbiology, and its essentiality for mammalian life was discovered in 1957. Independent and unrelated studies led to the identification of selenium as an integral constituent of one mammalian and two bacterial enzymes in the early 70ies followed by the identification of selenocysteine in these proteins. In the 80ies, independent sequencing of selenoproteins and cloned DNAs revealed that the selenocysteine of selenoproteins is encoded by the termination codon TGA (UGA). Recoding of TGA as selenocysteine codon by secondary mRNA structures was first elucidated by molecular genetics in bacteria and later in mammals. During the 90ies, finally, the basic principles of selenoprotein synthesis were worked out by molecular biology tools. The article closes with spotlight comments on proven and potential biomedical benefits of selenium and related research deficits.
本文回顾了一些偶然发现，这些发现促成了我们目前对硒在生物学中作用的认识。1818年，硒作为硫酸生产的副产品被发现，最初作为一种工业危害引起了医学关注。与此同时，硒中毒被认为是家畜疾病的病因。自上世纪中叶以来，陆续有关于硒的致畸作用和致癌性的报道。1954年，微生物学首次提供了关于硒特定生物学功能的线索，1957年发现硒对哺乳动物生命至关重要。独立且不相关的研究在70年代初导致硒被鉴定为一种哺乳动物酶和两种细菌酶的组成成分，随后在这些蛋白质中鉴定出硒代半胱氨酸。80年代，硒蛋白和克隆DNA的独立测序表明，硒蛋白中的硒代半胱氨酸由终止密码子TGA（UGA）编码。细菌中的分子遗传学首先阐明了通过二级mRNA结构将TGA重新编码为硒代半胱氨酸密码子，随后在哺乳动物中也得到了阐明。最终在90年代，通过分子生物学工具确定了硒蛋白合成的基本原理。文章最后重点评论了硒已证实的和潜在的生物医学益处以及相关的研究不足。
