放射性碘化丙硫氧嘧啶与大鼠肝脏微粒体组分的结合。甲状腺素5'-脱碘酶底物的刺激作用。
Binding of radioiodinated propylthiouracil to rat liver microsomal fractions. Stimulation by substrates for iodothyronine 5'-deiodinase.
作者信息
Visser T J, Van Overmeeren E
出版信息
Biochem J. 1979 Oct 1;183(1):167-9. doi: 10.1042/bj1830167.
Previous studies have shown that 2-thiouracil derivatives are uncompetitive inhibitors of iodothyronine 5'-deiodinase activity of rat liver microsomal fraction. Therefore the interaction of radioiodinated 6-propyl-2-thiouracil with rat liver microsomal fraction and the effect of substrate, cofactor and other inhibitors of 5'-deiodinase activity activity were investigated. It was found that micromolar concentrations of, in order of increasing potency, 3,5-diiodotyrosine, thyroxine, 3,3',5'-tri-iodothyronine and 3',5'-di-iodothyronine significantly enhanced binding of 5-[125I]iodo-6-propyl-2-thiouracil to the enzyme preparation. This stimulation was not seen in the presence of 1 mM dithiothreitol, 0.1 mM-6-propyl-2-thiouracil, 0.1 mM-6-propyl-2-thiouracil, 0.1 M-2-mercapto-1-methylimidazole or 1 mM-sodium sulphite. These results support the hypothesis that thiouracil derivatives inhibit 5'-deiodinase activity by forming a mixed disulphide with an intermediate enzyme complex, probably a sulphenyl iodide.
先前的研究表明，2-硫尿嘧啶衍生物是大鼠肝脏微粒体部分碘甲状腺原氨酸5'-脱碘酶活性的非竞争性抑制剂。因此，研究了放射性碘化的6-丙基-2-硫尿嘧啶与大鼠肝脏微粒体部分的相互作用以及底物、辅因子和其他5'-脱碘酶活性抑制剂的作用。结果发现，微摩尔浓度的3,5-二碘酪氨酸、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（按效力递增顺序）显著增强了5-[125I]碘-6-丙基-2-硫尿嘧啶与酶制剂的结合。在存在1 mM二硫苏糖醇、0.1 mM - 6-丙基-2-硫尿嘧啶、0.1 mM - 6-丙基-2-硫尿嘧啶、0.1 M - 2-巯基-1-甲基咪唑或1 mM亚硫酸钠的情况下未观察到这种刺激作用。这些结果支持了以下假设：硫尿嘧啶衍生物通过与中间酶复合物（可能是硫苯基碘化物）形成混合二硫化物来抑制5'-脱碘酶活性。
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