Thyroglobulin

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). 

Bioassay. Although the chemical assays described above have replaced bioassays for the determination of T and T, several m vivo and in vitro bioassays are used to determine the potency of thyroglobulin preparations and to estabUsh the thyromimetic or antithyroid potency of new compounds. 

ChEs possess the a/ 3-fold structure, which is shared with other esterases and non-catalytic proteins such as thyroglobulin, glutactin, neurotactin, gliotactin and neuroligins, all of these include a single ChE domain. Both ChEs are ellipsoidal molecules of 45-60-65 A3. Their structure consists of a central, highly twisted, 8-12-stranded (3-sheet, in which most strands are parallel, flanked on both sides by a-helices. Studies have indicated three major domains within the protein ... 

Thyroid-associated ophthalmopathy (TAO) is present in 90% of patients with the classical triad of Graves disease (goiter, ophthalmopathy, dermopathy) but these features may follow independent courses and successful control of the hyperthyroidism improves TAO in less than 5% cases. Immunosuppression has been used since theories of the etiology of TAO include the presence of circulating antibodies to both thyroid and ocular muscle fibers, and of thyroglobulin-antithy-roglobulin complexes with high affinity for extraocular muscles. 

Figure 42-11. Model of iodide metabolism in the thyroid follicle. A follicular cell is shown facing the follicular lumen (top) and the extracellular space (at bottom). Iodide enters the thyroid primarily through a transporter (bottom left). Thyroid hormone synthesis occurs in the follicular space through a series of reactions, many of which are peroxidase-mediated. Thyroid hormones, stored in the colloid in the follicular space, are released from thyroglobulin by hydrolysis inside the thyroid cell. (Tgb, thyroglobulin MIT, monoiodotyrosine DIT, diiodotyro-sine Tj, triiodothyronine T4, tetraiodothyronine.) Asterisks indicate steps or processes that are inherited enzyme deficiencies which cause congenital goiter and often result in hypothyroidism.

The coupling of two DIT molecules to form T4—or of an MIT and DIT to form T3—occurs within the thyroglobulin molecule. A separate coupfing enzyme has not been found, and since this is an oxidative process it is assumed that the same thyroperoxidase catalyzes this reaction by stimulating free radical formation of iodotyrosine. This hypothesis is supported by the observation that the same drugs which inhibit H oxidation also inhibit coupfing. The formed thyroid hor-... 

---