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Anionic iodotyrosine residues are required for iodothyronine synthesis.

Abstract：

:Biosynthesis of iodothyronines in thyroglobulin occurs by oxidative coupling of two iodotyrosine residues catalyzed by thyroperoxidase. To study the mechanism of iodothyronine formation, iodine-free thyroglobulin was non-enzymatically iodinated and after removal of non-incorporated iodide, incubated with lactoperoxidase and glucose oxidase between pH 4 and 9. The amount of thyroxine (T4). 3,5,3'-tri-iodothyronine (T3), 3,3',5'-tri-iodothyronine (rT3) and 3,3'-di-iodothyronine (T2) formed was measured by radioimmunoassays after hydrolysis of thyroglobulin. T4 is synthesized out of two di-iodotyrosine (DIT) residues in thyroglobulin. The pH dependence of T4 formation fits the dissociation curve of the DIT phenoxy group (pKa 6.5). The formation of T2, synthesized out of two mono-iodotyrosine (MIT) residues, shows a quite different pH dependence. Below pH 6, T2 synthesis could not be observed, while above pH 7.4 a relatively large increase occurred. The values up to pH 8 fitted the dissociation curve of the MIT-phenoxy group with a pKa of 8.7. The gradual loss in enzymatic activity of peroxidase and oxidase in the reaction made the values obtained above pH 8 unreliable. The importance of the ionization of the phenoxy group for the coupling reaction was further consolidated by showing that the pH-dependent oxidation of 2-methoxy-phenol (guaiacol) had 50% maximal product formation at pH 7, a value concordant with pKa 7.0 for the ionization of the phenoxy group of this agent. T3 and rT3 synthesis followed mainly the ionization curve of the inner-ring hydroxyl group, indicating that this ring has the greatest influence on hormonogenesis. Since anion formation facilitates the removal of an electron under oxidative conditions, the pH dependence agrees with the involvement of phenoxy radicals in iodothyronine synthesis, a process that most likely also occurs in vivo since it is mainly T4 that is formed in thyroglobulin.

journal_name

Eur J Endocrinol

journal_title

European journal of endocrinology

authors

de Vijlder JJ,den Hartog MT

doi

10.1530/eje.0.1380227

subject

Has Abstract

pub_date

1998-02-01 00:00:00

pages

227-31

issue

eissn

0804-4643

issn

1479-683X

journal_volume

138

pub_type

杂志文章

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Anionic iodotyrosine residues are required for iodothyronine synthesis.