3,3 ,5,5 -Tetraiodothyronine

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). 

Iodide ions and organic iodine compounds e.g. thyroxine, triiodo- and tetraiodothyronine... 

The amino acid tyrosine is the starting point in the synthesis of the catecholamines and of the thyroid hormones tetraiodothyronine (thyroxine T4) and triiodothyronine (T3) (Figure 42-2). T3 and T4 are unique in that they require the addition of iodine (as T) for bioactivity. Because dietary iodine is very scarce in many parts of the world, an intricate mechanism for accumulating and retaining T has evolved. 

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.

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. 

For electron-rich substrates, nature often uses flavin-dependent halogenases (e.g. chlorotetracycline), vanadium haloperoxidases (snyderol, Figure 7.4) or heme-iron haloperoxidases (tetraiodothyronine. Figure 7.4) for this role (Figure 7.5). For electron-deficient molecules such as alkanes, mononuclear iron... 

Dextrothyroxine Dextrothyroxine is D-3,3, 5,5 -tetraiodothyronine (25.1.10). The synthesis of this drug is described in Chapter 25. 

Hypothyroidism (myxedema) results when there is a breakdown of thyroid hormone production in the thyroid gland. Treatment consists of replacing this hormone with aforementioned drugs. Treatment with levothyroxine, 3,5,3, 5 -tetraiodothyronine, is preferred. Lyothyronin, L-3,5,5 -triiodothyronine, is also used, as is lotrix, a mixture of levothyroxine and levothyronine in a 4 1 ratio. Of the drugs of animal origin, thyroidin and thy-roglobulin (proloid) are used. 

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. 

Eukaryote organisms primarily respond to external signals by an initial signal perception by receptors. In general, such receptors can be either cytosolic or located on the plasma membrane [13-15]. The former mechanism applies to thyroid hormones (triiodothyronine and tetraiodothyronine or thyroxine), retinoids (e.g. retinoic acid), the insect developmental hormones such as ecdysone, steroid hormones (such as... 

Antagonists of riboflavin include isoriboflavin, lumiflavin, aiaboflavin, hydroxyethyl analogue, formyl methyl analogue, galactoflavin, and flavin-monosulfate. Synergists include vitamins A. B, B(l, and B12, niacin, pantothenic acid, folic acid, biotin, tetraiodothyronine (thyroxine), insulin, and somatotrophin (growth hormone). 

Therapeutic Function Thyroid hormone Chemical Name L-3,3, 5,5 -Tetraiodothyronine sodium salt Common Name -Structural Formula ... 

Abbreviations 3,5,3, 5 -tetraiodothyronine or thyroxine, T4 3,5,3-triiodothyronine, T, 3,3, 5 -triio-dothyronine, reverse T, or r-T3 3,5,3, 5 -tetraiodothyroacetic acid, TETRAC 3,5,3 -triiodothyroacetic acid, TRIAC 3,5-diiodotyrosine, DIT 3-monoiodotyrosine, MIT thyrotropic hormone, TSH thyreo-liberin, TRH growth hormone, GH microtubule associated proteins, MAPs TAU protein, one of the brain MAPs. 

Fig. 1. Major thyroid hormones (3,5,3 ,5 -tetraiodothyronine or thyroxine, T4) and (3,5,3 triiodothy-ronine, T,) and other important iodothyronines (3,3,5 -triiodothyronine or reverse-T, r-T and 3,3 -diiodothyronine 3,3 -T2). T4 and T, are active, r-Tj and 3,3 -T, are inactive. The acetic derivatives of T4 (TETRAC) and T, (TRIAC) are produced by oxidative decarboxylation of the alanine side-chain and have thyromimetic activities.

Abbreviations BAT, brown adipose tissue BrAc, /V-bromoacetyl- BSA, bovine serum albumin CNS, central nervous system DEP, diethylpyrocarbonatc DIT, diiodotyrosine DTT, dithiothreitol G, glu-curonide Grx, glutaredoxin GSH, reduced glutathione GSSG, oxidized glutathione IRD. inner ring deiodination MIT, monoiodotyrosine ORD, outer ring deiodination PTU, propylthiouracil S, sulfate rT3, 3,3, 5 -triiodothyronine (reverse T,) Trx, thioredoxin T2, diiodothyronine T3, 3,3, 5-triiodothyronine T4, 3,3, 5,5 -tetraiodothyronine (thyroxine). 

T, thymine T, threonine T3, triiodothyronine T4, tetraiodothyronine TBPS, ferft ary-butylbicyclophosphorothioate TGA, tricarboxylic acid TF, transcription factor TGI -fi, transforming growth factor (3 TGI -fi-Rs, transforming growth factor (3 receptors... 

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