Bioinorganic chemistry in thyroid gland: effect of antithyroid drugs on peroxidase-catalyzed oxidation and iodination reactions.

Gouriprasanna Roy,G Mugesh

doi:10.1155/bca/2006/23214

Gouriprasanna Roy, G Mugesh

Open Access

https://doi.org/10.1155/bca/2006/23214

Copy DOI

Abstract

Propylthiouracil (PTU) and methimazole (MMI) are the most commonly used antithyroid drugs. The available data suggest that these drugs may block the thyroid hormone synthesis by inhibiting the thyroid peroxidase (TPO) or diverting oxidized iodides away from thyroglobulin. It is also known that PTU inhibits the selenocysteine-containing enzyme ID-1 by reacting with the selenenyl iodide intermediate (E-SeI). In view of the current interest in antithyroid drugs, we have recently carried out biomimetic studies to understand the mechanism by which the antithyroid drugs inhibit the thyroid hormone synthesis and found that the replacement of sulfur with selenium in MMI leads to an interesting compound that may reversibly block the thyroid hormone synthesis. Our recent results on the inhibition of lactoperoxidase (LPO)-catalyzed oxidation and iodination reactions by antithyroid drugs are described.

Highlights

Thyroxine or 3,31⁄4,5,51⁄4-tetraiodothyronine (T4) is the major hormone secreted by the follicular cells of the thyroid gland
We show that the replacement of sulfur with selenium in MMI leads to an interesting compound (MSeI) that exhibits significant glutathione peroxidase (GPx)-like antioxidant activity
The reduction of H2O2 by 2 may become more efficient in the presence of suitable thiols such as GSH because this process may constitute a redox cycle involving a catalytic reduction of H2O2 (glutathione peroxidase (GPx) activity) [46]

Summary

INTRODUCTION

Thyroxine or 3,31⁄4,5,51⁄4-tetraiodothyronine (T4) is the major hormone secreted by the follicular cells of the thyroid gland This hormone is produced on thyroglobulin by thyroid peroxidase (TPO)/hydrogen peroxide/iodide system. The prohormone T4 is converted to its biologically active form T3 by an outer ring deiodination pathway This particular reaction is catalyzed by a selenocysteine-containing enzyme called iodothyronine deiodinase (ID-I), which is present in highest amounts in liver, kidney, thyroid, and pituitary [6,7,8,9,10,11,12,13,14,15,16]. The outer ring 51⁄4-deiodination catalyzed by the ID-I enzyme is considered to be the first step in thyroid hormone action because this is the only deiodination pathway that leads to the formation of an active thyroid hormone. As these antibodies are not under pituitary feedback control system, there is no negative influence on the thyroid activity and, the uncontrolled production of thyroid hormones leads

E Me N N H

Se1 C1 N2 C3

CONCLUSION AND OUTLOOK