Monoiodotyrosine , thyroid

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.

Several compounds can be oxidized by peroxidases by a free radical mechanism. Among various substrates of peroxidases, L-tyrosine attracts a great interest as an important phenolic compound containing at 100 200 pmol 1 1 in plasma and cells, which can be involved in lipid and protein oxidation. In 1980, Ralston and Dunford [187] have shown that HRP Compound II oxidizes L-tyrosine and 3,5-diiodo-L-tyrosine with pH-dependent reaction rates. Ohtaki et al. [188] measured the rate constants for the reactions of hog thyroid peroxidase Compounds I and II with L-tyrosine (Table 22.1) and showed that Compound I was reduced directly to ferric enzyme. Thus, in this case the reaction of Compound I with L-tyrosine proceeds by two-electron mechanism. In subsequent work these authors have shown [189] that at physiological pH TPO catalyzed the two-electron oxidation not only L-tyrosine but also D-tyrosine, A -acetyltyrosinamide, and monoiodotyrosine, whereas diiodotyrosine was oxidized by a one-electron mechanism. 

The iodinated tyrosine residues monoiodotyrosine (MIT) and diiodoty-rosine (DIT) combine (couple) to form iodothyronines in reactions catalyzed by thyroid peroxidase. Thus, two molecules of DIT combine to form T4, and MIT and DIT join to form T3. 

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...

The thyroid follicular cells transport I across the cell and secrete the precursor protein, Tg, into the follicular lumen. In addition, these cells contain an apical membrane-bound enzyme, thyroperoxidase (TPO), and the enzymatic machinery to produce hydrogen peroxide (H2O2). In the presence of H2O2, TPO catalyzes the incorporation of L into tyrosyl residues of Tg to form monoiodotyrosine (MIT) and diiodotyrosine (DIT) and the coupling of these iodotyrosyl residues to form T4 and Tj. 

Experimental design Groups of 8-11 male rats were treated with 0, 1, 3, or 6 mg/kg/day doses of an unspecified mixture of PBBs in lecithin liposomes by gavage for 10 days. Plasma was assayed on treatment days 10 and 20. Other end points were evaluated on treatment day 20 these included plasma TSH levels, 5-hour thyroid uptake of I, incorporation of into monoiodotyrosine, diiodotyrosine, I, or T4, amount of intrathyroidal iodide, thyroid and liver weights, and body weights. Differences between mean values for the measured parameters in the control and PBB-treated groups were analyzed with the Student s Mest, with aP value of 0.05 considered as statistically significant. 

Takatera and Watanabe [41] used this technique for the speciation of iodide ion, I-, and five iodo amino acids (monoiodotyrosine (MIT), diiodotyrosine (DIT), 3,3,5-triiodothyromine (T3), 3,3,5 -triiodothyromine (rT3), and thyroxine (T4)) which are all found in thyroid hormones. The speciation of these compounds in clinical samples such as blood plasma and urine may assist in the identification of thyroid diseases. The RPLC-ICP-MS system was able to detect all of the I-containing compounds with no interferences. Detection limits were in the range 35-130 pg for the six compounds using a 50% methanol eluent. Detection limits were better for species eluted at a shorter retention time since the peak shapes were sharper. The detection limits calculated were an order of magnitude lower than for methods where UV absorbance detection was used. 

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 thyroid protein, thyroglobulin, contains 3-monoiodotyrosine, 3,5-diiodotyrosine and several iodinated thyronine derivatives (Salvatore and Edelhoch 1973). lodohistidines may also be present in this protein. 3-Bromotyrosine has been reported in serum proteins (Firnau and Fritze 1972). Methods for separating and analyzing these and other halogenated tyrosines are presented in 2.2.3. 

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 52-1 Structure of thyroid hormones and their precursors. MIT, Monoiodotyrosine DiT, diiodotyrosine rTs, 3,3 5 -L-tri iodothyron ine Tj, 3,5,3 -L-tri iodothyroni ne T4, 3,5,3, 5 -L-tetraiodothyronine.

FIGURE 18.13 Thyroid hormones and their side products diiodotyrosine (DIT) and monoiodotyrosine (MIT) formed during their biosynthesis. 

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.

Figure 45-2. Biosynthesis of the thyroid hormones Tj and in the thyroid follicular cell and release into the bloodstream. Abbreviations are as follows TG, thyroglobulin MIT, monoiodotyrosine DIT, diiodotyrosine Tj, triiodothyronine T., thyroxine.

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.

The oxidation of intracellular iodide is catalyzed by thyroid peroxidase (located at the apical border of the thyroid acinar cell) in what may be a two-electron oxidation step forming 1 (iodinium ion), lodinium ion may react with a tyrosine residue in the protein thyroglobulin to form a tyrosine quinoid and then a 3 -monoiodotyrosine (MIT) residue. It has been suggested that a second iodide is added to the ring by similar mechanisms to form a 3,5-diiodotyrosine (DIT) residue. Because iodide is added to these organic compounds, iodination is also referred to as the organification of iodide. ... 

T3 and synthesis The thyroid follicular cell traps inorganic iodide and oxidizes it to iodine. Iodine binds to tyrosine residues of thyroglobulin to form monoiodotyrosine (MIT) and diiodotyrosine (DIT). Then, either two DIT molecules couple to form T or MIT couples with DIT, forming T3. T production exceeds T3 production in the thyroid gland and T is converted to T3 in the periphery. 

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... 

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.

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