Effect of iodide concentration on thyroxine synthesis catalysed by thyroid peroxidase.

Abstract

Thyroglobulin with a low content of iodine atoms per molecule of protein was incubated with thyroid peroxidase and increasing iodine concentrations (0.01 to 4 mM). When iodide was in great excess (4 mM), I2 was the only product, protein iodination being markedly or completely inhibited. At low iodide concentrations (0.2 mM and below) no I2 was formed. A clear competition between these two possible reactions catalysed by thyroid peroxidase was therefore demonstrated. When iodide concentration was less than 0.5 mM, thyroid peroxidase catalysed only the iodination of thyroglobulin. Thyroid hormones began to accumulate when the iodination reaction leveled off. Different observations suggest that thyroxine was synthesised mainly by the coupling of two diiodotyrosine residues rather than by the iodination of 3,5,3′‐triiodothyronine residues. With very low iodide concentration, the synthesis of hormones began soon after the formation of hormonogenic residues. However the iodination reaction being faster than the coupling reaction, highly iodinated thyroglobulin could be obtained which did not contain thyroid hormones. From these results it appears that thyroid peroxidase is able to enter into at least three reactions: iodide peroxidation, tyrosine residues iodination and coupling of iodotyrosine residues to thyroid hormones. Surprisingly, this relative unspecificity of thyroid peroxidase may have some regulatory physiological significance.