的作用机制的thioureylene抗甲状腺药物。
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Taurog一
的作用机制的thioureylene抗甲状腺药物。
内分泌学。1976年4月,98(4):1031 - 46所示。
- PubMed ID
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1278093 (在PubMed]
- 文摘
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孵化系统模型包含净化甲状腺过氧化物酶(TPO)被用来研究thioureylene甲状腺药物的作用机理——丙基硫氧嘧啶(PTU) methylmercapto咪唑(MMI)和卡比马唑。两种类型的实验进行:1)测量的抑制性影响药物TPO-catalyzed碘化和TPO-catalyzed愈创木酚氧化,和b)研究PTU的新陈代谢和MMI TPO模型系统。主要的观察可以概括如下:1)TPO-catalyzed thioureylene药物有效的抑制剂的蛋白质和酪氨酸的碘化。他们的力量大大增强I -的浓度减少。2)thioureylene药物也强有力的抑制剂TPO-catalyzed愈创木酚的氧化,不涉及碘化反应。3)MMI和PTU很容易氧化碘化模型中孵化系统存在但不缺乏碘。氧化的速率增加碘的浓度是妈妈从10增加到100。4)氧化PTU和MMI模型孵化系统是由相对轻微的抑制浓度的增加PTU和MMI。这些药物能够抑制自己和对方的新陈代谢。5)抑制碘化是由碘引起竞争力较低的药物浓度,但不是在较高的药物浓度。 6) Inhibition of iodination by MMI and PTU may be either reversible (low ratio of drug to iodide), or irreversible (higher ratio of drug to iodide). In reversible inhibition the iodination is inhibited for a period which may be as brief as 2 min or as long as 20 min, but thereafter, iodination begins, and there is escape from inhibition. During the lag-period there is extensive metabolism of the drug. In the case of irreversible inhibition of iodination is inhibited completely or almost completely for 60 min, and drug oxidation during this period is relatively low. 7) Irreversible inhibition may be transformed into reversible inhibition by increasing the concentration of TPO or the concentration of iodide. However, increasing the concentration of H2O2 or of tyrosine does not overcome irreversible inhibition. On the basis of these findings and of current views concerning the mechanism of enzymatic iodination, a scheme is proposed for the mechanism of inhibition by thioureylene drugs of TPO-catalyzed iodination of protein and tyrosine.