Thyronines iodinated

G15. Gyde, O. H. B., Hirst, A. D., and Howorth, P. J. N., An improved method for the mechanised estimation of thyronine-iodine by the bromine-displacement technique. Clin. Chim. Acta 45, 443-447 (1973). 

The thyroid hormones T3 and T4 are unique in that iodine (as iodide) is an essential component of both. In most parts of the world, iodine is a scarce component of soil, and for that reason there is htde in food. A complex mechanism has evolved to acquire and retain this cmcial element and to convert it into a form suitable for incorporation into organic compounds. At the same time, the thyroid must synthesize thyronine from tyrosine, and this synthesis takes place in thyroglobuhn (Figure 42-11). 

Triiodothyronine is not classified as a thyroid inhibitor it is an amino acid derivative of thyronine and results from the oxidative coupling of monoiodotyrosyl and diiodotyrosyl residues. Iodine 131, the most often used radioisotope of I, is rapidly absorbed by the thyroid and is deposited in follicular colloid. Prom the site of its deposition, Bll causes fibrosis of the thyroid subsequent to pyknosis and necrosis of the follicular cells. 

Thyroxine (57) was rapidly photodeiodinated by light filtered to give wavelengths above 300 nm. In the first few minutes the main product was 3,3, 5-triiodothyronine, but by 15 min, 3,5-diiodothyronine and 3-iodothyronine were present in major amounts. There were also traces of 3,3, 5-triiodothyronine and 3,3 -diiodothyronine. In some runs traces of 3,3, 5 -triiodothyronine and 3, 5 -diiodothyronine were detected. Over 30 min the main product was 3-iodothyronine. Further deiodination to thyronine was very slow, presumably because the UV spectra had lower-wavelength maxima as iodine was removed. Similar photolysis of 3,3, 5-triiodothyronine for 10 min also gave 3,5-diiodo-... 

The hormone triiodothyronine (T3) accelerates both total energy expenditure and protein degradation. The hormone secreted by the thyroid gland is thyroxine, which is converted to the active hormone T3 in a process that removes an iodine atom from the 5 position of the thyronine ring. If, however, an iodine atom is removed from the 3 position, the result is the formation of reverse-Ts... 

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. 

It has been observed that non-iodinated thyronine is not found in the thyroid gland. 

Synthesis L-diiodo thyronine (1.05 g) is dissolved in ammonia (specific gravity 0.880) (40 ml) and methanol (40 ml) and iodinated slowly with shaking with N-iodine in KI solution at room temperature. After iodination,... 

Thyroid hormone synthesis requires oxidation of dietary iodine, followed by iodination of tyrosine to mono- and diiodotyrosine coupling of iodotyrosines leads to formation of the active molecules, tetraiodo-tyrosine, (T or L-th3rroxine) and triiodotyrosine (Tj or L-thyronine). 

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. 

Figure 52-2 Hypothalamic-pituitary-thyroid axis—hormone synthesis dependent on dietary intake of ISO pg of iodine per day.T4 major thyronine secreted from thyroid gland with T3 coming predominantly from peripheral deiodination.

The biosynthesis of thyroid hormones involves the trapping of circulating iodide (iodide transport) by the thyroid gland, the incorporation of iodine into tyrosine, and the coupling of iodinated tyrosyl residues to form the thyronines (T4 and... 

Degradative studies suggested the presence of two benzene rings, a phenolic oxygen, an ether oxygen, and an alanine side chain. Of the possible structures, that now accepted for thyronine was considered most likely and was proved by synthesis (350). The position of the iodine... 

The generic term thyroid hormones refers to the iodinated amino acid derivatives T3 (3,3, 5-triiodo-L-thyronine) and T4 (3,3, 5,5 -tetraiodo-L-thyronine), the only iodinated hormones produced endogenously. T3 is the biologically active hormone and is, for the most part, produced from T4 in extrathyroidal tissues. T4 lacks significant bioactivity and is a hormone precursor however,... 

The basic structure of T3 and T4 is that of thyronine, a substituted tyrosine [0-(4-hydroxyphenyl)tyrosine] (Figure 33-1). Iodine residues at positions 3 and 5 of the inner phenolic ring confer on the outer ring a preferred orientation approximately 120° to the plane of the inner ring (Figure 33-2). Hormonal activity is maximal when the following requirements are met ... 

Iodine is present at positions 3 and 5 of the inner ring (required for receptor binding). A natural analog of T3, called reverse T3 (rT3, 3,3, 5 -triiodo-L-thyronine), is inactive. Substitution of iodine by bromine... 

Structure of 3,3, 5,5 -tetraiodo-L-thyronine (T4). T4 is a substituted tyrosine or a diphenylether derivative of alanine. Positions in the outer phenolic ring have prime designations, in contrast to those in the inner ring. T4 is iodinated at positions 3 and 5 in both rings. [Modified and reproduced with permission from V. Cody, Thyroid hormone interactions molecular conformation, protein binding, and hormone action. Endocr. Rev. 1,140 (1980). (c)1980by the Endocrine Society.]... 

Primary or secondary aliphatic amines in aqueous or methanolic solution may replace the ammonia, for these do not form explosive iodo derivatives.468,469 This method can be recommended for preparative purposes and has proved very valuable in the preparation of thyroxine from 3,5-diiodo-thyronine in 20% aqueous ethylamine (KI3), of thyroxine methyl ester from 3,5-diiodothyronine methyl ester in 1 2 butylamine-methanol (I2)4 9 and of 3,5-diiodotyrosine in 20% aqueous ethylamine (Nal3),470 as well as in iodination... 

Lankmayr, E.P. Budna, K.W. Nachtmann, F. Separation of enantiomeric iodinated thyronines by liquid chromatography of diastereomers. J.Chromatogr., 1980, 198, 471-479... 

Buch BERGER W, Holler W and Winsauer K (1990) Effects of sodium bromide on the biosynthesis of thyroid hormones and brominated/iodinated thyronines. J Trace Elem Electrolyte Health Dis 4 25-30. 

The principal hormones of the thyroid gland are iodine-containing amino add derivatives of thyronine and U Figure 56-1). is a prohormone that is converted to the biologically... 

It has been suggested that treatment with supraphysiologic levels of iodine has potential therapeutic uses beyond thyronine function (Miller, 2006). Some clinicians believe that all tissues in the human body should be saturated with iodine (Flechas, 2005). Maintenance of the equilibrium between thyroidal and extrathyroidal iodine is estimated to require about six times the tolerable upper intake level (UL) (Berson and Yalow, 1954). Controlled chronic safety data for daily iodine intake at these levels are difficult to find even though physicians prescribed daily iodine therapy at doses that ranged from 10 to 100 times the UL during the first half of the twentieth century (Kelly, 1961). 

Thyronine—receptor complexes stimulate or inhibit gene expression in almost every tissue in the human body, and therefore necessarily command our focus. The result is a thyroid hormone (TH)-centric perspective of iodine physiology that persuades us to avoid consideration of nonthyronine pharmacologic activity associated with iodine. The role for so-called extrathyroidal iodine has been discussed in the hterature as iodide uptake in the majority of breast cancers has aroused the interest of several researchers (Venturi et at. 

A large number of clinical and nonclinical studies demonstrate that iodine exerts pharmacological activity unrelated to thyronine. The most thoroughly examined area relates to the mechanism underlying the autoregulatory effect in the thyroid. A second area of research that has received attention is the effect of iodine on the mammary tissue. These two areas are briefly reviewed here as they provide insight into the cfinical data that will subsequently be discussed. 

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