Mechanism of iodide-dependent catalatic activity of thyroid peroxidase and lactoperoxidase.
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.
D000818:Animals; D002374:Catalase / Q000378:metabolism; D002417:Cattle; D006861:Hydrogen Peroxide / Q000378:metabolism; D007453:Iodide Peroxidase / Q000378:metabolism*; D007454:Iodides / Q000494:pharmacology*; D007784:Lactoperoxidase / Q000378:metabolism*; D008713:Methimazole / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism*; D013552:Swine; D013861:Thiocyanates / Q000494:pharmacology
D007454:Iodides; D013861:Thiocyanates; D008713:Methimazole; D006861:Hydrogen Peroxide; D007784:Lactoperoxidase; D010544:Peroxidases; D002374:Catalase; D007453:Iodide Peroxidase; D010100:Oxygen; C009941:potassium thiocyanate