Magnusson R P, Taurog A, Dorris M L
J Biol Chem. 1984 Jan 10;259(1):197-205.
Mechanisms that have been proposed for peroxidase-catalyzed iodination require the utilization of 1 mol of H2O2 for organic binding of 1 mol of iodide. When we measured the stoichiometry of this reaction using thyroid peroxidase or lactoperoxidase at pH 7.0, we consistently obtained a ratio less than 1.0. This was shown to be attributable to catalase-like activity of these enzymes, resulting in unproductive cleavage of H2O2. This catalatic activity was completely iodide-dependent. To elucidate the mechanism of the iodide-dependent catalatic activity, the effects of various agents were investigated. The major observations may be summarized as follows: 1) The catalatic activity was inhibited in the presence of an iodine acceptor such as tyrosine. 2) The pseudohalide, SCN-, could not replace I- as a promoter of catalatic activity. 3) The inhibitory effects of the thioureylene drugs, methimazole and carbimazole, on the iodide-dependent catalatic activity were very similar to those reported previously for thyroid peroxidase-catalyzed iodination. 4) High concentrations of I- inhibited the catalatic activity of thyroid peroxidase and lactoperoxidase in a manner similar to that described previously for peroxidase-catalyzed iodination. On the basis of these observations and other findings, we have proposed a scheme which offers a possible explanation for iodide-dependent catalatic activity of thyroid peroxidase and lactoperoxidase. Compound I of the peroxidases is represented as EO, and oxidation of I- by EO is postulated to form enzyme-bound hypoiodite, represented in our scheme as [EOI]-. We suggest that the latter can react with H2O2 in a catalase-like reaction, with evolution of O2. We postulate further that the same form of oxidized iodine is also involved in iodination of tyrosine, oxidation of thioureylene drugs, and oxidation of I-, and that inhibition of catalatic activity by these agents occurs through competition with H2O2 for oxidized iodine.
关于过氧化物酶催化碘化反应所提出的机制，需要利用1摩尔的H2O2来实现1摩尔碘化物的有机结合。当我们在pH 7.0条件下使用甲状腺过氧化物酶或乳过氧化物酶测量该反应的化学计量关系时，始终得到小于1.0的比率。结果表明，这是由于这些酶具有过氧化氢酶样活性，导致H2O2发生非生产性裂解。这种催化活性完全依赖于碘化物。为了阐明碘化物依赖性催化活性的机制，研究了各种试剂的作用。主要观察结果可总结如下：1）在存在碘受体如酪氨酸的情况下，催化活性受到抑制。2）拟卤化物SCN-不能替代I-作为催化活性的促进剂。3）硫脲类药物甲巯咪唑和卡比马唑对碘化物依赖性催化活性的抑制作用与先前报道的甲状腺过氧化物酶催化碘化反应的抑制作用非常相似。4）高浓度的I-以类似于先前描述的过氧化物酶催化碘化反应的方式抑制甲状腺过氧化物酶和乳过氧化物酶的催化活性。基于这些观察结果和其他发现，我们提出了一个方案，该方案为甲状腺过氧化物酶和乳过氧化物酶的碘化物依赖性催化活性提供了一种可能的解释。过氧化物酶的化合物I表示为EO，推测EO将I-氧化形成酶结合的次碘酸盐，在我们的方案中表示为[EOI]-。我们认为后者可以在类似过氧化氢酶的反应中与H2O2反应，释放出O2。我们进一步推测，相同形式的氧化碘也参与酪氨酸的碘化、硫脲类药物的氧化以及I-的氧化，并且这些试剂对催化活性的抑制是通过与H2O2竞争氧化碘而发生的。
