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硫脲使碘甲状腺原氨酸5'-脱碘酶失活的底物需求。

Substrate requirement for inactivation of iodothyronine-5'-deiodinase activity by thiouracil.

作者信息

Visser T J, van Overmeeren-Kaptein E

出版信息

Biochim Biophys Acta. 1981 Apr 14;658(2):202-8. doi: 10.1016/0005-2744(81)90290-4.

Abstract

Preincubation of rat liver microsomal fraction with 1 microM 2-thiouracil and 0.01-1 microM 3,3',5'-triiodothyronine or 3',5'-diiodothyronine, 0.1-10 microM thyroxine or 3,5-diiodothyronine led to a progressive, irreversible and concomitant decrease in subsequently assayed 3,3',5'-triiodothyronine- and 3',5'-diiodothyronine-5'-deiodinase activity. Preincubation with thiouracil alone, with iodothyronines alone or with thiouracil and 10 microM thyronine or 3,5-diiodotyrosine had no or virtually no effect. The results indicate that (1) a previously proposed ping-pong mechanism for thyroid hormone deiodination, involving the formation of an enzyme-sulphenyl iodide intermediate, is correct; (2) thyroxine, 3,3',5'-triiodothyronine and 3',5'-diiodothyronine are substrates for a common 5'-deiodinase; (3) this 5'-deiodinase is not fully specific as regards the position of the iodine substituents in the substrate, since it also appears to catalyse the 5-deiodination of 3,5-diiodothyronine.

摘要

将大鼠肝微粒体部分与1微摩尔2-硫脲以及0.01 - 1微摩尔3,3',5'-三碘甲状腺原氨酸或3',5'-二碘甲状腺原氨酸、0.1 - 10微摩尔甲状腺素或3,5-二碘甲状腺原氨酸预孵育,会导致随后检测的3,3',5'-三碘甲状腺原氨酸和3',5'-二碘甲状腺原氨酸5'-脱碘酶活性逐渐、不可逆且同时降低。单独用硫脲预孵育、单独用碘甲状腺原氨酸预孵育或用硫脲与10微摩尔甲状腺原氨酸或3,5-二碘酪氨酸预孵育均无或几乎没有影响。结果表明:(1) 先前提出的涉及形成酶-亚磺酰碘中间体的甲状腺激素脱碘乒乓机制是正确的;(2) 甲状腺素、3,3',5'-三碘甲状腺原氨酸和3',5'-二碘甲状腺原氨酸是一种共同的5'-脱碘酶的底物;(3) 这种5'-脱碘酶对底物中碘取代基的位置并非完全特异性,因为它似乎也催化3,5-二碘甲状腺原氨酸的5-脱碘反应。

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