Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases.
Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases.
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DOI：
10.1210/edrv.23.1.0455
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发表时间：
2002-02
影响因子：
20.3
通讯作者：
A. Bianco;D. Salvatore;B. Gereben;Marla J. Berry;P. Larsen
中科院分区：
文献类型：
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作者：
A. Bianco;D. Salvatore;B. Gereben;Marla J. Berry;P. Larsen
这篇综述的目的是将我们对1、2和3型(分别为D1、D2和D3)碘甲状腺原氨酸脱碘酶的分子生物学方面所取得的令人振奋的进展放在生化和生理的背景下。我们综述了有关硒蛋白合成机制、单个脱碘酶的分子和细胞生物学特性的新数据，包括基因结构、mRNA和蛋白质特征、组织分布、亚细胞定位和拓扑、酶特性、构效关系以及合成、失活和降解的调节。这些都为讨论它们在人类和其他脊椎动物甲状腺生理中的作用提供了背景，包括证据表明D2在人类血浆T(3)的产生中发挥着重要作用。我们讨论了D3过度表达导致“消耗性甲状腺功能减退症”的病理作用，以及我们目前对疾病期间碘甲状腺原氨酸脱碘和胺碘酮治疗的病理生理学的理解。最后，我们回顾了对Dio2基因的靶向破坏和D2在心肌中过表达的小鼠的分析的新见解。
The goal of this review is to place the exciting advances that have occurred in our understanding of the molecular biology of the types 1, 2, and 3 (D1, D2, and D3, respectively) iodothyronine deiodinases into a biochemical and physiological context. We review new data regarding the mechanism of selenoprotein synthesis, the molecular and cellular biological properties of the individual deiodinases, including gene structure, mRNA and protein characteristics, tissue distribution, subcellular localization and topology, enzymatic properties, structure-activity relationships, and regulation of synthesis, inactivation, and degradation. These provide the background for a discussion of their role in thyroid physiology in humans and other vertebrates, including evidence that D2 plays a significant role in human plasma T(3) production. We discuss the pathological role of D3 overexpression causing "consumptive hypothyroidism" as well as our current understanding of the pathophysiology of iodothyronine deiodination during illness and amiodarone therapy. Finally, we review the new insights from analysis of mice with targeted disruption of the Dio2 gene and overexpression of D2 in the myocardium.