他巴唑体外抑制酪氨酸碘化的机制

The mechanism of action of methimazole in inhibiting the iodination of tyrosyl residues in bovine serum albumin

目的 探讨抗甲状腺药物的作用机制。方法 ①在甲状腺过氧化物酶（ＴＰＯ）中加入他巴唑、碘化钾、过氧化氢，然后进行透析，用３，３，５，５，四甲基联苯胺（ＴＭＢ）测ＴＰＯ的活性；②在ＴＰＯ催化酪氨酸碘化的反应体系中，加入他巴唑，并逐渐增加过氧化脲的浓度，观察过氧化脲浓度对他巴唑干扰酪氨酸碘化的影响。结果 ＴＰＯ中加入他巴唑，与加入磷酸盐缓冲液（ＰＢ）对照，经透析后，两者酶活性没有明显的区别。在ＴＰＯ催化的酪氨酸碘化的反应体系中，提高过氧化脲的浓度，能抵消他巴唑对酪氨酸碘化的抑制作用。结论 他巴唑对ＴＰＯ无直接抑制作用，其作用机制是夺去酪氨酸碘化所必需的活性氧（他巴唑本身被氧化）从而抑制甲状腺素的合成。

AIM To investigate the mechanism of action of Methimazole in inhibiting iodination of tyrosyl residues in bovine serum albumin. METHODS ①Purified the thyroid peroxidase from the thyroid specimen removed from patient with Graves disease and established the TPO urea hydrogen peroxide(UHP) catalysed tyrosine(in BSA) iodination system.② Incubated rough TPO(rTPO) or dialyzed TPO(dTPO) with methimazole and/or potassium iodide in 37℃ for 12 hours,then dialyzed against 0 1 mmol·L -1 PB, and determined the absorbance at 700 nm after adding hydrogen peroxide and 3,3,5,5 tetramethylbenzidine(TMB). ③Increased the concentration of UHP in BSA tyrosine iodination system and measured the radioactivity of iodinated tyrosine. RESULTS TPO activity had no significant deference between rTPO+PB, rTPO+methimazole and dTPO+methimazole +potassium iodide+hydrogen peroxide. While added hydrogen peroxide into dTPO(with or without addition of methimazole), the TPO activity decreased sharply( P <0 01)except those which potassium iodide were added into. In BSA tyrosine iodination system the methimazoles inhibition was reduced by the increment of the concentration of UHP. CONCLUSION methimazole consume the active oxygen that is required for tyrosine iodination,which consequently results in the decrement of thyroxine synthesis, and has no direct inhibition on TPO activity.