Iodine containing thyroid hormones

Dioxins, PCBs and Iodine Effects on Synthesis and Metabolism of the Iodine Containing Thyroid Hormones... 

Iodine is essential for the normal development of all animals and man. Its basic biological importance is indicated by the fact that the tadpole will not undergo metamorphosis into the frog without the function of the thyroid gland in secreting the iodine-containing thyroid hormones. 

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). 

Thiocyanate ion, SCN , inhibits formation of thyroid hormones by inhibiting the iodination of tyrosine residues in thyroglobufin by thyroid peroxidase. This ion is also responsible for the goitrogenic effect of cassava (manioc, tapioca). Cyanide, CN , is liberated by hydrolysis from the cyanogenic glucoside finamarin it contains, which in turn is biodetoxified to SCN. 

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. 

Thyroid hormone an iodine-containing amino acid that affects the action of the thyroid gland. 

Thyroxine one of the iodine-containing amino acids that act as a thyroid hormone. 

The thyroid hormone thyroxine (tetraiodo-thyronine, T4) and its active form triiodothyronine (T3) are derived from the amino acid tyrosine. The iodine atoms at positions 3 and 5 of the two phenol rings are characteristic of them. Post-translational synthesis of thyroxine takes place in the thyroid gland from tyrosine residues of the protein thyro-globulin, from which it is proteolytically cleaved before being released, iodothyronines are the only organic molecules in the animal organism that contain iodine. They increase the basal metabolic rate, partly by regulating mitochondrial ATP synthesis, in addition, they promote embryonic development. 

Figure 8.17. Structure of the iodine-containing amino acid-based thyroid hormones—thyroxine and triiodothyronine...

The thyroid hormones T4 and T3 contain 65% and 59% of iodine respectively as an essential component for biological activity of the molecule. Iodine from dietary sources or medication enters the body via gastrointestinal tract. The recommended daily adult intake is 150-300 pg. Iodine is rapidly absorbed and enters the extracellular fluid pool. Iodide is removed from the blood largely by the thyroid and kidneys. The higher the intake the lower the fractional iodine uptake by the thyroid. 

Three hormones, thyroxine (3,5,3, 5 -tetraiodothy-ronine, or T4), triiodothyronine (3,5,3 -triiodothyronine, or T3), and calcitonin (see Chapter 66) are secreted by the thyroid gland. The hormones T4 and Tj are iodine-containing amino acid derivatives and are unique in that they have no discrete target tissue. Every tissue in the body is affected in some way by thyroid hormones, and almost all cells appear to require constant optimal amounts for normal operation. 

A normal rate of thyroid hormone synthesis depends on an adequate dietary intake of iodine. Iodine is naturally present in water and soil, although some soils contain very low amounts. As a result, seafood is a more reliable source of iodine than crop plants. Approximately 1.6 billion people in more than 100 countries live in areas where natural sources of dietary iodine intake are marginal or insufficient. A minimum of 60 j.g of elemental iodine is required each day for thyroid hormone synthesis, and at least 100 j.g/day is required to eliminate thyroid follicular cell hyperplasia and thyroid enlargement (i.e., iodine deficiency goiter). 

T4, T3, MIT, and DIT are stored outside the cell in the follicular colloid in peptide linkage within the Tg molecules. In normal humans on an iodine-sufficient diet, Tg makes up approximately 30% of the mass of the thyroid gland and represents a 2- to 3-month supply of hormone. The total amount of iodine contained as T4, T3, MIT, and DIT within Tg varies with the dietary iodine intake. 

In humans, the major pathway in the metabolism of the thyroid hormones consists of the removal of iodine or deiodination. Three deiodinase isoenzymes, encoded on three distinct genes, catalyze the reductive deiodination. All three enzymes contain the rare amino acid seleno-cysteine. The essential trace element selenium therefore plays an important role in thyroid hormone economy. 

The total thyroid hormone content of thyroid glands and the ratio of T3 to T4 vary somewhat from one species to another. Thyroid USP preparations are therefore standardized on the basis of their iodine content. Much of the iodine in these preparations is in the metabolically inactive form of iodotyrosines. Thus, a given preparation may satisfy the USP iodine assay requirements and yet contain low amounts of T4 and T3. Thyrar (a beef extract) and Armour Thyroid tablets (a pork extract) are evaluated by additional biological assays to ensure consistent potency from one batch to another. 

The normal thyroid gland secretes sufficient amounts of the thyroid hormones—triiodothyronine (T3) and tetraiodothyronine (T4, thyroxine)—to normalize growth and development, body temperature, and energy levels. These hormones contain 59% and 65% (respectively) of iodine as an essential part of the molecule. Calcitonin, the second type of thyroid hormone, is important in the regulation of calcium metabolism and is discussed in Chapter 42. 

Although large numbers of organohalogens are known, very few of them occur naturally. Thyroid hormones (e.g., thyroxine) that contain iodine... 

The iodine-containing cream was withdrawn and she was given a beta-blocker. The palpitation resolved within 2 weeks and her plasma thyroid hormone concentrations normalized within 1 month. 

A 48-year-old woman developed palpitation and insomnia. The clinical history, physical examination, and laboratory tests supported hyperthyroidism. Since July 1994 she had been combating constipation by improper use of an iodine-containing antiseptic cream for external use only. She had inserted povidone-iodine into her rectum by means of a cannula. The iodine-containing cream was withdrawn and she was given a beta-blocker. The palpitation resolved within 2 weeks and her plasma thyroid hormone concentrations normalized within 1 month. 

Thyroid hormone-producing thyroid carcinoma is an uncommon cause of thyrotoxicosis. Precipitation of thyrotoxicosis by iodine-containing compounds in patients with thyroid carcinoma is rare, but has been attributed to amiodarone in a 77-year-old man with extensive hepatic metastases from a well-differentiated thyroid carcinoma (40). 

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