| Thyroxine and tri-iodothyronine
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| T 4 is produced exclusively in the thyroid gland and is more abundant than T 3, which is the biologically active form
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| Figure 37.6 Structures of the thyroid hormones T4, T3, and rT3. |
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| T4 (also known as tetra-iodothyronine) and T3 are structurally simple molecules, being iodinated thyronines produced by the coupling of a phenyl group detached from one tyrosine to the phenyl group of a second intact tyrosine (Fig. 37.6). The biosynthesis of T4 and T3 occurs within thyroglobulin, a large (660 kDa) glycoprotein that accounts for about 75% of the protein content of the thyroid gland. Iodination of thyroglobulin occurs late after it has been secreted
into the follicular lumen. The secretion of T4 and T3 requires enzymatic hydrolysis of thyroglobulin, which is located in the follicular colloid. During hydrolysis and subsequent deiodination, the released iodide is conserved and reutilized. About 25 mg of thyroglobulin are hydrolyzed daily for production of ∼100 μg of T4.
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| Thyroid hormone bioactivity is regulated by controlling the conversion of T4 into T 3 by deiodination; this is mediated by three deiodinase enzymes
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| T4 is quantitatively the most important thyroid hormone and it is produced exclusively by the thyroid gland. T3 is the biologically active form of thyroid hormone produced by 5'- deiodination of T4. This process may occur in the thyroid gland, in target tissues, or in other peripheral tissues, and is accomplished by iodothyronine deiodinases I and II. The type I enzyme regulates plasma T3 levels, while the type II enzyme controls nuclear T3 levels. The type III enzyme is the major catabolic enzyme; it catalyzes the removal of an iodide from the 5- rather than 5'-position, resulting in reverse T3, which is inactive. Thus, control of the deiodination of T4 is one method of controlling thyroid hormone bioactivity (see Fig. 37.6). About 80% of T4 is metabolized by deiodination with about equal amounts of T3 and rT3 being produced. The remaining T4 is conjugated with sulfate or glucuronic acid and deactivated by deamidation or decarboxylation.
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| The biologically active fraction of T3 and T4 in plasma (free T3 or free T4i.e. a fraction which is not bound to protein) represents, in each case, less than 1% of the total concentration of the hormone
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| The daily production of T4 is approximately 10% of the extrathyroidal pool, much of which is bound to TBG or albumin in plasma. Approximately 80% of this T4 is converted to T3 by extrathyroidal deiodination. The turnover of T3 is much greater than that of T4. The biologically active component of T4 and T3 in plasma is the free fraction - that not bound to proteins. This fraction, which is a measure of thyroid hormone status, represents <1% of the total T4 and T3.
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