Thyroglobulin iodination

Wildberger E, Kohler H, Jenzer H, et al Inactivation of Peroxidase and Glucose Oxidase by H202 and Iodide during In Vitro Thyroglobulin Iodination. Mol Cell Endocrinol 1986 46(2) 149-154. 

IIIG) 1975 Gurel, Demet Dynamics of Thyroglobulin Iodination, 5th Int. Biophysics Congress, Copenhagen, Abstract P-438, p. 124... 

Thyroid Hormones. Iodine, absorbed as P, is oxidized in the thyroid and bound to a thyroglobulin. The resultant glycoprotein, mol wt 670,000, contains 120 tyrosine residues of which ca two-thirds are available for binding iodine in several ways. Proteolysis introduces the active hormones 3,5,3 -triiodothyronine (T ) and 3,5,3, 5 -tetraiodothyronine (T, (thyroxine) in the ratio Ty.T of 4 1 (121,122). 

Organification Binding of iodine to tyrosine residues of thyroglobulin. 

Derived from the amino acid tyrosine, thyroid hormones are unique because they contain iodine. At this time, its incorporation into thyroid hormones is the only known use for iodine in the body. There are two thyroid hormones, named for the number of iodides added to the tyrosine residues of the thyroglobulin triiodothyronine (T3) and tetraiodothyronine (T4, thyroxine). Although significantly more T4 is synthesized by the thyroid gland, T3 is the active hormone. At the target tissue, T4 is deiodoninated to form the more potent T3. 

Amiodarone may induce thyrotoxicosis (2% to 3% of patients) or hypothyroidism. It interferes with type I 5 -deiodinase, leading to reduced conversion of T4 to T3, and iodide release from the drug may contribute to iodine excess. Amiodarone also causes a destructive thyroiditis with loss of thyroglobulin and thyroid hormones. 

Many environmental factors have been implicated in the induction of autoimmunity. One dietary component, iodine, has been well studied as a factor that increases autoimmune thyroid disease.67 68 Based on studies in the OS chicken, the increasing prevalence of autoimmune thyroid disease observed in U.S. and Western European populations has been ascribed to increased use of iodized salt.69 Experimentally, it can be shown that iodinated thyroglobulin is a more potent autoantigen than the equivalent noniodinated molecule. Food additives or pesticides may also be important in contributing to the development of autoimmune disease in susceptible individuals.70... 

Thyroxine is actually a simple derivative of the aromatic amino acid tyrosine (see Section 13.1), but is believed to be derived by degradation of a larger protein molecule containing tyrosine residues. One hypothesis for their formation invokes suitably placed tyrosine residues in the protein thyroglobulin being iodinated to di-iodotyrosine. These residues then react together by phenolic oxidative coupling. 

As the human body is able to store many minerals, deviations from the daily ration are balanced out over a given period of time. Minerals stored in the body include water, which is distributed throughout the whole body calcium, stored in the form of apatite in the bones (see p. 340) iodine, stored as thyroglobulin in the thyroid and iron, stored in the form of ferritin and hemosiderin in the bone marrow, spleen, and liver (see p. 286). The storage site for many trace elements is the liver. In many cases, the metabolism of minerals is regulated by hormones—for example, the uptake and excretion of H2O, Na, ... 

Iodine is used pre-operatively and in the management of thyrotoxic crisis. It temporarily inhibits proteolysis of thyroglobulin and prevents the release... 

Thyroid epithelial cells synthesize and secrete T4 and T3 and make up the functional units of thyroid glandular tissue, the thyroid follicles. Thyroid follicles are hollow vesicles formed by a single layer of epithelial cells that are filled with colloid. T4,T3, and iodine are stored in the follicular colloid. T4 and T3 are derived from tyrosyl residues of the protein thyroglobulin (Tg). Thyroid follicular cells synthesize and secrete Tg into the follicular lumen. Thyroid follicular cells also remove iodide (I ) from the blood and concentrate it within the follicular lumen. Within the follicles, some of the tyrosyl residues of Tg are iodinated, and a few specific pairs of iodoty-rosyl residues may be coupled to form T4 and T3. Thus, T4, T3, and iodine (in the form of iodinated tyrosyl residues) are found within the peptide structure of the Tg that is stored in the follicular lumen. 

Thyroid Hormones The thyroid hormones T4 (thyroxine) and T3 (triiodothyronine) are synthesized from the precursor protein thyroglobulin (Mr 660,000). Up to 20 Tyr residues in thyroglobulin are enzymatically iodinated... 

An important product of tyrosine metabolism in vetebrates is the thyroid hormone101 of which the principal and most active forms are thyroxine (T4) and triiodothyronine (T3).102 The thyroid gland is rich in iodide ion, which is actively concentrated from the plasma to 1 pM free I. 103 This iodide reacts under the influence of a peroxidase (see Fig. 16-14 and accompanying discussion)104 to iodinate tyrosyl residues of the very large 660-kDa dimeric thyroglobulin, which is stored in large amounts in the lumen of the... 

Thyroxine (T4) and the more potent triiodothyronine (T3) are cleaved from a large precursor protein called thyroglob-ulin. Thyroglobulin exists as a dimer of two identical polypeptides (Mr 330,000). It is a storage protein for iodine and can be considered a prohormone of the circulating thyroid hormones. Thyroglobulin is secreted into the lumen of the thyroid gland, where specific residues are iodinated in... 

Thyroid cells actively transport iodine (I-), which is incorporated into a few tyrosine residues of thyroglobulin by the enzyme iodoperoxidase. After condensation of iodinated tyrosine residues, the thyroglobulin is proteolytically degraded liberating thyroxine and triiodothyronine. 

Radioactive isotopes of iodine are handled by the thyroid in the same way as stable iodine and are therefore actively concentrated, incorporated into thyroglobulin, stored, metabolized, and secreted as thyroid hormones. Small amounts of radioactive iodine are therefore ideal probes to analyse the uptake of iodine, the distribution of iodine in the gland, and possibly even its turnover and incorporation into thyroid hormones. Larger amounts of radioactive iodine selectively radiate the thyroid gland and therefore selectively impair the function of the follicular thyroid cells and eventually destroy them. 

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