Triiodothyronine synthesis

Triiodothyronine (3, 5,3-L-triiodothyronine, T3) is a thyroid hormone. It is producedby outer ring deiodination of thyroxine (T4) in peripheral tissues. The biologic activity of T3 is 3-8 times higher than that of T4. T3 is 99.7% protein-bound and is effective in its free non-protein-bound form. The half-life of triiodothyronine is about 19 h. The daily tur nover of T3 is 75%. Triiodothyronine acts via nuclear receptor binding with subsequent induction of protein synthesis. Effects of thyroid hormones are apparent in almost all organ systems. They include effects on the basal metabolic rate and the metabolisms of proteins, lipids and carbohydrates. 

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.

FIGURE 41-1. Hypothalamic-pituitary-thyroid axis. Thyrotropinreleasing hormone (TRH) is synthesized in the neurons within the paraventricular nucleus of the hypothalamus. TRH is released into the hypothalamic-pituitary portal circulation and carried to the pituitary, where it activates the pituitary to synthesize and release thyrotropin (TSH). TSH activates the thyroid to stimulate the synthesis and secretion of thyroxine (T4) and triiodothyronine (T3). T4 and T3 inhibit TRH and TSH secretion, closing the feedback loop. 

The concentration of Li+ in the thyroid is three to four times that in serum [179]. It is thought that Li+ may be concentrated in the thyroid gland by a mechanism similar to the incorporation of iodide, I-, resulting in competition between Li+ and I the levels of intracellular 1 decrease when those of Li+ increase, and vice versa [182]. Li+ inhibits both the ability of the gland to accumulate 1 and the release of iodine from the gland. In vitro, Li+ has no effect on thyroid peroxidase, the enzyme that catalyzes the incorporation of I" into tyrosyl residues leading to thyroidal hormone synthesis, but does increase the activity of iodotyrosine-deio-dinase, which catalyzes the reductive deiodination of iodotyrosyls, thus maintaining the levels of intracellular I [182]. The increase in iodoty-rosine-deiodinase activity is probably a response to the Li+-induced decrease in the concentration of thyroidal I". Li+ has no effect on the conversion of thyroxine to triiodothyronine. The overall effect of this competition between Li+ and 1 is, therefore, reduced levels of thyroid hormone in the presence of Li+. 

Figure 12.8 Effector mechanism activation of a specific gene by hormone-receptor complex binding to DNA. A steroid is used to illustrate the mechanism. The hormone enters the cell and binds to its receptor (R) in the cytosol, the hormone-receptor complex enters the nucleus and binds to a specific sequence in the DNA that stimulates transcription of a gene or genes the resultant increase in mRNA increases the synthesis of specific proteins. The binding site on the DNA is specific and is usually termed a response element. Thyroxine (i.e. triiodothyronine) also uses this effector mechanism. Activation of genes, RNA processing to produce mRNA and translation are described in Chapter 20 (see Figures 20.20, 20.21 and 20.22).

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. 

Traube purine synthesis, 423 Triamcinolone, 201 Triamcinolone acetonide, 201 Triamterine, 427 Triazines, synthesis, 280 Triazolam, 368 Trichlomethiazide, 359 Trichomonas, 238 Tricyclic antidepressants, 149 Trifluoperidol, 306 Trifluoromethyl group, potentiation of biologic activity, 380 Triflupromazine, 380, 381 Trihexyphenidil, 47 Triiodothyronine, 95 Trimeprazine, 378 Trimethadione, 232 Trimethobenzamide, 110 Trimethoprim, 262 Trioxsalen, 334 Tripelenamine, 51 Triprolidine, 78 Tropinone, 5 Tropocaine, 7 Truth serum, 274... 

Thioamides are reducing agents. They inhibit thyroid hormone synthesis by inhibiting the peroxidase enzymatic system, which catalyzes oxidation of iodide ions and iodine that are consumed in food, which is necessary for iodination of tyrosine derivatives. Thus they reduce the concentration of free iodine necessary to react with tyrosine derivatives, and they can also block oxidative addition reactions of mono- and diiodtyrosines, which form L-thyroxine and L-triiodothyronin. 

Amiodarone inhibits the peripheral and possibly in-trapituitary conversion of thyroxine (T4) to triiodothyronine (Tj) by inhibiting 5 -deiodination. The serum concentration of T4 is increased by a decrease in its clearance, and thyroid synthesis is increased by a reduced suppression of the pituitary thyrotropin T3. The concentration of T3 in the serum decreases, and reverse T3 appears in increased amounts. Despite these changes, most patients appear to be maintained in an euthyroid state. Manifestations of both hypothyroidism and hyperthyroidism have been reported. 

Mechanism of Action A synthetic form of triiodothyronine (T3), a thyroid hormone involved in normal metabolism, growth, and development. Possesses catabolic and anabolic effects. Therapeutic Effect Increases basal metabolic rate, enhances gluco-neogenesis, and stimulates protein synthesis. 

Mecfianism of Action A thiourea derivative that blocks oxidation of iodine in the thyroid gland and blocks synthesis of thyroxine and triiodothyronine. Therapeutic Effect Inhibits synthesis of thyroid hormone. 

Lithium blocks the release of thyroxine (T4) and triiodothyronine (T3) mediated by thyrotropin (Kleiner et ah, 1999). This results in a decrease in circulating T4 and T3 concentrations and a feedback increase in serum thyrotropin concentration. It also inhibits thyrotropin-stimulated adenylate cyclase activity (Kleiner et ah, 1999). Lithium has varying effects on carbohydrate metabolism. Increased and decreased glucose tolerance and decreased sensitivity to insulin have been observed (Van derVelde Gordon, 1969). In animals, lithium decreases hepatic cholesterol and fatty acid synthesis. 

Sodium and potassium iodides find limited use as expectorants but a much more important use is as additives, at levels around 5—100 fig/g to table salt in many countries as a prophylactic against goitre. This is a condition arising from iodine deficiency with the result that there is insufficient synthesis of the iodine-containing amino acids, thyroxine and 3,3, 5-triiodothyronine, that are essential components of the... 

The culture system used in this study has proven suitable for studying the regulation, especially by hormones, of myelina-tion in vitro. Initial studies (35-36), however, showed no effect of 3, 5, 3 -triiodothyronine (T,) on sulfolipid synthesis by dissociated brain cells grown on medium containing 20% calf... 

The thyroid gland synthesizes two primary hormones thyroxine and triiodothyronine. A discussion of the synthesis and function of these hormones follows. 

The activities of a variety of flavin-dependent enzymes are depressed in hypothyroidism. They are increased by the administration of thyroxine or triiodothyronine, as a result of increased synthesis of riboflavin phosphate and... 

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