Davidson B, Soodak M, Neary J T, Strout H V, Kieffer J D, Mover H, Maloof F
Endocrinology. 1978 Sep;103(3):871-82. doi: 10.1210/endo-103-3-871.
A reinvestigation of the mechanism of action of methylmercaptoimidazole, propylthiouracil, and thiouracil on thyroid peroxidase (TPO) was undertaken. A preliminary incubation of TPO and H2O2 with methylmercaptoimidazole, propylthiouracil, or thiouracil was carried out in the absence of oxidizable substrates (i.e. I- or guaiacol). This incubation resulted in irreversible inactivation of TPO. The extent of inactivation could be determined after removal of the drug by gel filtration or by dilution into the assay mixture. Preincubation, as above, in the presence of iodide or thiocyanate prevented the irreversible inactivation of TPO. Rats receiving doses of these drugs which completely inhibited protein-bound iodine formation showed normal levels of TPO in their thyroid glands 30 min after drug administration. These findings suggest that the initial in vivo action of these drugs is to block iodination by trapping oxidized iodide, not by acting as "general inhibitors" of the TPO.
对甲巯基咪唑、丙硫氧嘧啶和硫氧嘧啶作用于甲状腺过氧化物酶（TPO）的作用机制进行了重新研究。在不存在可氧化底物（即碘离子或愈创木酚）的情况下，将TPO和过氧化氢与甲巯基咪唑、丙硫氧嘧啶或硫氧嘧啶进行预孵育。这种孵育导致TPO不可逆失活。通过凝胶过滤或稀释到测定混合物中去除药物后，可以确定失活程度。如上述在碘化物或硫氰酸盐存在下进行预孵育可防止TPO的不可逆失活。接受完全抑制蛋白结合碘形成剂量这些药物的大鼠在给药30分钟后甲状腺中TPO水平正常。这些发现表明，这些药物在体内的初始作用是通过捕获氧化碘来阻断碘化作用，而不是作为TPO的“一般抑制剂”起作用。
