TYPE-I IODOTHYRONINE DEIODINASE IS A SELENOCYSTEINE-CONTAINING ENZYME
TYPE-I IODOTHYRONINE DEIODINASE IS A SELENOCYSTEINE-CONTAINING ENZYME
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DOI：
10.1038/349438a0
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发表时间：
1991-01-31
期刊：
影响因子：
64.8
通讯作者：
LARSEN, PR
中科院分区：
文献类型：
--
作者：
BERRY, MJ;BANU, L;LARSEN, PR
尽管甲状腺素（3,5,3',5'-四碘甲状腺原氨酸，T4）是脊椎动物甲状腺的主要分泌产物，但其重要的代谢和发育作用均由 3,5,3'-三碘甲状腺原氨酸（T3）介导，3,5,3'-三碘甲状腺原氨酸（T3）是由激素原通过 5'-脱碘产生的。 I 型碘甲状腺原氨酸脱碘酶是一种需要硫醇的丙基硫氧嘧啶敏感氧化还原酶，主要存在于肝脏和肾脏中，并提供大部分循环 T3(1)，但迄今为止该酶尚未纯化。通过在非洲爪蟾卵母细胞中进行表达克隆，我们从大鼠肝脏 cDNA 文库中分离出了该脱碘酶的 2.1 KB 互补 DNA。 瞬时测定系统中表达的蛋白质的动力学特性、信使 RNA 的组织分布及其随甲状腺状态的变化都证实了其身份。 我们发现这种酶的 mRNA 含有硒代半胱氨酸的 UGA 密码子，这是最大酶活性所必需的。 这解释了为什么在实验性缺硒中 T4 向 T3 的转化受到损害 2-6，并确定了这种微量元素在甲状腺激素作用中的重要作用。
ALTHOUGH thyroxine (3,5,3',5'-tetraiodonthyroine, T4) is the principal secretory product of the vertebrate thyroid, its essential metabolic and developmental effects are all mediated by 3,5,3'-triiodothyronine (T3), which is produced from the prohormone by 5'-deiodination. The type-I iodothyronine deiodinase, a thiol-requiring propylthiouracil-sensitive oxidoreductase, is found mainly in liver and kidney and provides most of the circulating T3(1) but so far this enzyme has not been purified. Using expression cloning in the Xenopus oocyte, we have isolated a 2.1-kilobase complementary DNA of this deiodinase from a rat liver cDNA library. The kinetic properties of the protein expressed in transient assay systems, the tissue distribution of the messenger RNA, and its changes with thyroid status, all confirm its identity. We find that the mRNA for this enzyme contains a UGA codon for selenocysteine which is necessary for maximal enzyme activity. This explains why conversion to T4 to T3 is impaired in experimental selenium deficiency 2-6 and identifies an essential role for this trace element in thyroid hormone action.