Monoiodotyrosine , thyroid hormone synthesis

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.

Fig. 1 Thyroid hormone synthesis in a thyroid follicular cell. NIS and TPO (organification and coupling reaction) have been marked in red dashed line as the two main targets for direct thyroid gland function disrupters. DEHALl iodotyrosine dehalogenase 1, DIT diiodotyrosine, DUOX2 dual oxidase 2, MIT monoiodotyrosine, Na/K-ATPase sodium-potassium ATPase, NIS sodium-iodide symporter, PSD pendrin, TG thyroglobulin, TPO thyroperoxidase. Reprinted from [7] with permission from Elsevier...

Figure 24.1 Thyroid follicle, thyroid oell, and thyroid hormone synthesis. NIS, sodium/iodide symporter PDS, pendrin TG, thyroglobulin TPO, thyroid peroxidase DUOX2, dual oxidase type 2 MIT, monoiodotyrosine DIT, diiodotyrosine T4, thyroxine T3, triiodothyronine DEHAL1, dehalogenase 1.

Fig. 43.10. Synthesis of the thyroid hormones (T3 and T4). The protein thyroglobulin (Tgb) is synthesized in thyroid follicular cells and secreted into the colloid, lodination and coupling of tyrosine residues in Tgb produce T3 and T4 residues, which are released from Tgb by pinocytosis (endocytosis) and lysosomal action. The coupling of a monoiodotyrosine with a diiodotyrosine (DIT) to form triiodothyronine (Tj) is not depicted here.

Iodine is an essential element in humans and other mammals, which is used for the synthesis of the thyroid hormones triiodothyronine (T3) and thyroxine (T4). These hormones play a prominent role in the metabolism of most cells of the organism and in the process of early growth and development of most organs, especially brain (Anderson et al., 2000). Besides T3 and T4, reverse T3 (rT3), monoiodotyrosine (MIT), and diiodotyrosine (DIT) are also synthesized and distributed in the body of humans and animals, but only T3 and T4 have a biological function. Iodine in the human body mainly comes through dietary and water intake, and inhalation of atmospheric iodine. Due to low concentrations of iodine in the air (10—20ng/m ), food and water intake form the major source of iodine for adults, while for infants it is milk. The concentration of iodine in foodstuffs is directly related to that in the environment where the foods come from. Iodine deficiency disorders are mainly found in places where the concentration of iodine in the soil and drinking water is very low. In the water, foodsmffs, and... 

With regard to the fate of the iodinated amino acids in the thyroid, the following concluraons have been reached. Monoiodotyrosine and diiodotyrosine do not leave the thyroid gland after proteolytic hydrolysis of thyroglobulin, but are enzymically deiodinated with the formation of iodide this iodide is available for re-utilization in hormone synthesis. Thyroxine and triiodothyronine are released into the circulation. 

Triiodothyronine and thyroxine are the physiologically active hormones of the thyroid gland. Tyrosine is the starting material for their synthesis. Gries and co-workers [62] have chromatographed thyroid-active iodoamino acids on cellulose G layers and obtained good separations of DL-thyroxine, DL-truodothyroxine, DL-diiodothyronine, dl-monoiodothyronine, diiodotyrosine and monoiodotyrosine. 

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