33’3’-Triiodothyronine, structure

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

The structural formulas of thyroxine and triiodothyronine as well as reverse triiodothyronine (rT3) are shown in Figure 38-2. 

The chemical structures of thyroxine and triiodothyronine are shown in Figure 31—1. As shown in the figure, thyroid hormones are synthesized first by adding iodine to residues of the amino acid tyrosine. Addition of one iodine atom creates monoiodotyrosine, and the addition of a second iodine creates diiodotyrosine. Two of these iodinated tyrosines are then combined to complete the thyroid hormone. The combination of a monoiodotyrosine and a diiodotyrosine yields triiodothyronine, and the combination of two diiodoty-rosines yields thyroxine.55... 

FIGURE 31-1 Structure of the thyroid hormones triiodothyronine (T3] and thyroxine (T4X Addition of one iodine atom [I] to tyrosine produces monoiodotyrosine addition of a second iodine atom produces diiodotyrosine. A monoiodotyrosine and diiodotyrosine combine to form triiodothyronine (T3X Coupling of two diiodotyrosines forms thyroxine (T4X... 

The structural formulas of thyroxine and triiodothyronine as well as reverse triiodothyronine (rT3) are shown in Figure 38-2. All of these naturally occurring molecules are levo (L) isomers. The synthetic dextro (D) isomer of thyroxine, dextrothyroxine, has approximately 4% of the biologic activity of the L isomer as evidenced by its lesser ability to suppress TSH secretion and correct hypothyroidism. 

This skewed conformation also imparts further stereospecific characteristics to the hormone T3 which contains only a single outer ring iodine. Because of the restricted rotation about the two diphenyl ether bonds, the chemically equivalent 3 and 5 -iodines are conformationally distinct, giving rise to a distal (away) or proximal (near) conformation (Figure 3). To verify the importance of this conformational feature, numerous structural analogues of triiodothyronine were synthesized (4) in an effort to determine the biologically active conformer of T. ... 

The thyroid gland secretes two hormones, thyroxine (3,5,3, 5 -L tetraiodothyronine) and triiodothyronine (3,5>3 -L-triiodothyronine), which are commonly known as T4 and T3, respectively (Table 52-1). In addition, the thyroid gland secretes small amounts of biologically inactive 3,3, 5 -L-triiodothyronine (reverse T3 [rTa]) and minute quantities of monoiodotyrosine (MIT) and diiodotyrosine (DIT), which are precursors of T3 and T4. The structures of these compounds are shown in Figure 52-1. 

Figure 3.7 Structural resemblance between triiodothyronine and a hydroxylated PBDE metabolite.

The thyroid hormones thyroxine (T4) and triiodothyronine (T3) are formed on thyroglobulin, a large glycoprotein synthesized within the thyroid cell (Fig. 73-1). Because of the unique tertiary structure of... 

Figure 45-1. Structures of the thyroid hormones thyroxine (T ) and triiodothyronine (Tj). Also shown are the intermediates monoiodotyrosine (MIT) and diiodotyrosine (DIT) that are also formed on thyroglobulin.

The thyroid gland secretes the thyroid hormones tetraiodothyronine (T4) and triiodothyronine (T3) (see Fig. 11.8 for the structure of T3). T3 is the most active form of the hormone. T4 is synthesized and secreted in approximately 10 times greater amounts than T3. Hepatocytes (liver cells) and other cells contain a deiodi-nase that removes one of the iodines from T4, converting it to T3. T3 exerts its effects on tissues by regulating the transcription of specific genes involved in energy metabolism (see Chapter 16, section III.C.2., Fig. 16.14). 

Figure 15.6 Structure of iodinated hormones and their metabolism prooess. Thyroxin (T4) synthesized in the thyroid was deiodinated in the blood and tissues by 5-deiodinase to 3,5, 3 -triiodothyronine (rT3> and by 5 -deiodinase to 3,5,3 -triiodothyronine (Ts). vvhich is then further deiodinated by 5-deiodinase to diiodothyronine (T2)-...

As soon as radioactive tracers of iodine, especially iodide, thyroxine (T4), and triiodothyronine (T3), became available after the end of World War II, research began on the kinetics of radioiodine in humans, as well as in experimental animals. As measuring devices improved, radioactivity could be measured not only in the blood plasma, but also in other body fluids, and external measurement of the radioactivity in the thyroid and in other organs of the body soon became feasible. A rich body of experimental data ensued there was a need to synthesize these data into a unifying theoretical structure. 

Drugs The most common source of iodine excess in the United States is amiodarone, a widely used antiarrhythmic drug. Amiodarone contains 37% iodine and shows a structural similarity with the thyroid hormones triiodothyronine (T3) and tetraiodothyronine (T4) (Hermann, 2004 Kennedy et al, 1989 Martino et al, 2001). 

The thyroid gland is a highly vascular, flat structure located at the upper portion of the trachea, just below the larynx. It is composed of two lateral lobes Joined by an isthmus across the ventral surface of the trachea. The gland is the source of two fundamentally different types of hormones, thyroxine (T4) and triiodothyronine (T3). Both hormones are vital for normal growth and development and control essential functions, such as energy metabolism and protein synthesis. 

Mahaux JE, Chamla-Soumenkoff J, Delcourt R, et al. The effect of triiodothyronine on cervical lymphoid structures, thyroid activity, IgG and IgM immunoglobulin level, and exophthalmos in Graves disease. Acta Endocrinol 1969 61 400-406. 

Chopra IJ, Chua Teco GN, Eisenberg JB, et al. Structure-activity relationships of inhibition of hepatic monodeiodination of thyroxine to 3,5,3 -triiodothyronine by thiouracil and related compounds. Endocrinology 1982 110 163-168. 

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