Open AccessFree Diiodotyrosine Effects on Protein Iodination and Thyroid Hormone Synthesis Catalyzed by Thyroid Peroxidase
Author(s) -
DÈME Danièle,
FIMIANI Enzo,
POMMIER Jacques,
NUNEZ Jacques
Publication year - 1975
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1975.tb03932.x
Subject(s) - diiodotyrosine , thyroid peroxidase , chemistry , thyroglobulin , iodide , peroxidase , iodine , thyroid , biochemistry , endocrinology , hormone , triiodothyronine , inorganic chemistry , enzyme , organic chemistry , biology
Free diiosotyrosine exerts two opposite effects on the reactions catalyzed by thyroid peroxidase, thyroglobulin iodination and thyroid hormone formation.1 Inhibition of thyroglobulin iodination catalyzed by thyroid peroxidase was observed when free diiodotyrosine concentration was higher than 5 μM. This inhibition was competitive, suggesting that free diiodotyrosine interacts with the substrate site(s) of thyroid peroxidase. Free diiodotyrosine also competitively inhibited iodide peroxidation to I 2 . 2 Free diiodotyrosine, when incubated with thyroid peroxidase in the absence of iodide was recovered unmodified; in the presence of iodide an exchange reaction was observed between the iodine atoms present in the diiodotyrosine molecule and iodide present in the medium. Using 14 C‐labelled diiodotyrosine, 14 C‐labelled non‐iodinated products were also observed, showing that deiodination occurred as a minor degradation pathway. However, no monoiodo[ 14 C]tyrosine or [ 14 C]tyrosine were observed. Exchange reaction between free diiototyrosine and iodide is therefore direct and does not imply deiodination‐iodination intermediary steps. Thyroglobulin inhibits diiodotyrosine‐iodide exchange and vice versa , again suggesting competition for both reactions. These results support, by a different experimental approach, the two‐site model for peroxidase previously described by us in this journal. 3 Free diiodotyrosine when present at a very low concentration, 0.05 μM, exerts a stimulatory effect on thyroid hormones synthesis. The relationship between diiodotyrosine concentration and thyroid hormone synthesis give an S‐shaped curve, suggesting that free diiodotyrosine acts as a regulatory ligand for thyroid peroxidase. Evidence is also presented that free diiodotyrosine is not incorporated into thyroid hormones. Therefore, thyroid peroxidase catalyzes only intra‐molecular coupling between iodotyrosine hormonogenic residues. 4 Finally, although no direct proof exists that these free diiodotyrosine effects upon thyroglobulin iodination and thyroid hormone synthesis are physiologically significant, such a possibility deserves further investigation.