Hormonal Thyroxine

Amino acid-derived hormones include the catecholamines, epinephrine and norepinephrine (qv), and the thyroid hormones, thyroxine and triiodothyronine (see Thyroid AND ANTITHYROID PREPARATIONS). Catecholamines are synthesized from the amino acid tyrosine by a series of enzymatic reactions that include hydroxylations, decarboxylations, and methylations. Thyroid hormones also are derived from tyrosine iodination of the tyrosine residues on a large protein backbone results in the production of active hormone. 

The thyroid hormones thyroxine (T4) and triiodothyronine (T3) are formed on thyroglobulin, a large glycoprotein synthesized within the thyroid cell. Inorganic iodide enters the thyroid follicular cell and is oxidized by thyroid peroxidase and covalently bound (organified) to tyrosine residues of thyroglobulin. 

In addition to neutral loss scans, mass spectrometers can be used to detect other compounds in a different manner. Acylcamitines are fatty acid esters of carnitine. The masses of acylcamitines differ by the size of the fatty acid attached to it. The tandem mass spectrometer can detect these selectively as well because they all produce a similar product, in this case an ion rather than a molecule. Because it is an ion, it can be detected by the second mass separation device. The ion has a mass of 85 Da and is common to all acylcamitines. Performing a precursor ion scan of 85 Da (essentially a scan of only molecules that produce the 85 ion) reveals a selective analysis of acylcar-nitines, as shown in Fig. 14.2. Additional scans have been added to more selectively detect basic amino acids, free carnitine, short chain acylcamitines and a hormone, thyroxin (T4) which has amino acid components. 

Figure 1.5 The thyroid hormones thyroxine and triiodothyronine are produced by the action of iodoperoxidase and subsequent proteolysis of thyroglobin. (From Voet and Voet, 2004. Reproduced with permission from John Wiley Sons., Inc.)...

Tyrosine (Tyr or Y) (4-hydroxyphenylalanine ((5)-2-amino-3-(4-hydroxyphenyl)-propanoic acid)) is a polar, neutral, aromatic amino acid with the formula H00CCH(NH2)CH2C6H50H and is the precursor of thyroxin, dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), and the pigment melanin. Being the precursor amino acid for the thyroid gland hormone thyroxin, a defect in this may result in hypothyroidism. Tyr is extremely soluble in water, a property that has proven useful in isolating this amino acid from protein hydrolysates. The occurrence of tyrosine- 0-sulfate as a constituent of human urine and fibrinogen has been reported. ... 

Iodine is essential in the mammalian diet to produce the thyroid hormone thyroxine deficiency in humans causes goitre. Collectively, deficiencies of iodine, iron, zinc and vitamin A in humans are thought to be at least as widespread and debilitating as calorie deficiencies (Welch and Graham, 1999). The main source of iodine in soils is oceanic salts rather than parent rock, and so deficiency is most widespread in areas remote from the sea (Fuge, 1996). In principle deficiency is easily corrected with dairy supplements. However in practice this is not always feasible. Addition of iodate to irrigation water has successfully corrected widespread iodine deficiency in parts of China where the usual methods of supplementation had failed (Cao et al., 1994 Jiang et al 1997). However there is not much information on the behaviour of iodine in soil and water systems. 

Thyroid Hormone (Thyroxine, Synthroid). The most common use of thyroxine in bipolar patients is the treatment of lithium-induced hypothyroidism. Approximately 5% of patients receiving long-term lithium treatment ultimately develop hypothyroidism. When this occurs, the patient with bipolar disorder may present with symptoms of a depressive episode. Therefore, periodic thyroid axis monitoring, that is, a serum thyroid stimulating hormone (TSH) test, is required for all patients taking lithium and should always be performed when the bipolar patient experiences a depressive episode. 

Other hormones Thyroxine has long been known to increase metabolic rate, although the mechanism for this effect is not totally clear (Silvestri et al. 2005). More recently the hormone leptin, which is secreted by adipose tissue, has also been found to increase the metabolic rate. This effect of leptin is considered to play a role in controlling the amount of adipose tissue in the body, although this is a controversial subject (Chapter 12). 

Trace amounts of iodine are required for a healthy body. Iodine is part of the hormone thyroxin produced by the thyroid gland. Thyroid secretions control the physical and mental development of the human body. A goiter, a swelling of the thyroid gland, is caused by the lack of iodine. Adding thyroid medication and iodized salt to the diet helps prevent this disease. Radioactive iodine (1-131), with a half-life of eight days, is used to treat some diseases of the thyroid gland. 

The thyroid hormone thyroxine is necessary for the development and function of cells throughout the body. It increases protein synthesis and oxygen consumption in almost all types of body tissue. Excess thyroxine causes hyperthyroidism, with increased heart rate, blood pressure, overactivity, muscular weakness, and loss of weight. 

Transport. A wellknown transport protein is hemoglobin in the erythrocytes (bottom left). It is responsible for the transport of oxygen and carbon dioxide between the lungs and tissues (see p.282). The blood plasma also contains many other proteins with transport functions. Prealbumin (transthyretin middle), for example, transports the thyroid hormones thyroxin and triiodothyronine. Ion channels and other integral membrane proteins (see p.220) facilitate the transport of ions and metabolites across biological membranes. 

The albumin fraction also includes transthyretin (prealbumin), which together with other proteins transports the hormone thyroxine and its metabolites. 

The substance to be assayed—e.g., the hormone thyroxine in a serum sample—is pipetted into a microtiter plate (1), the walls of which are coated with antibodies that specifically bind the hormone. At the same time, a small amount of thyroxine is added to the incubation to which an enzyme known as the "tracer" (1) has been chemically coupled. The tracer and the hormone being assayed compete for the small number of antibody binding sites available. After binding has taken place (2), all of the unbound molecules are rinsed out. The addition of a substrate solution for the enzyme (a chromogenic solution) then triggers an indicator reaction (3), the products of which can be assessed using photometry (4). 

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. 

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

Three hormones, thyroxine (3,5,3, 5 -tetraiodothy-ronine, or T4), triiodothyronine (3,5,3 -triiodothyronine, or T3), and calcitonin (see Chapter 66) are secreted by the thyroid gland. The hormones T4 and Tj are iodine-containing amino acid derivatives and are unique in that they have no discrete target tissue. Every tissue in the body is affected in some way by thyroid hormones, and almost all cells appear to require constant optimal amounts for normal operation. 

Levothyroxine (also marketed as Levoxyl, Levothroid, Synthroid, or L-thyroxine sodium) is the only thyroid system prescription that has recently featured prominently among the top 200 medications in the United States. Thus, 75.1 million, 80.7 million, and 79.4 million levothyroxine prescriptions were dispensed in 2003, 2004, and 2005, respectively. At these rates, levothyroxine by itself comprised 3.5, 2.9, and 3.4% of the total prescriptions in the top 200 most popular drugs in the United States in 2003, 2004, and 2005, respectively, making it the most prescribed drug. Levothyroxine is a synthetic version of the natural hormone thyroxine, which is released by the thyroid gland. The natural hormone is important in the development of fetuses and newborns, playing a role in cmcial processes such as the development... 

Thyroid gland secretes two important hormones, thyroxine (TJ and triiodothyronine (Tj). The third hormone, calcitonin secreted from interstitial cells is physiologically different and is responsible for the regulation of calcium metabolism. 

The thyroid gland secretes two iodinated hormones, thyroxin (T4) and triiodothyronine (T3). The thyroid contributes only about 20% of the unbound circulating T3. The remainder is produced by the... 

In contrast, steroid hormones, thyroxine, and retinoids bind to internal receptors. In 1968, Gorski et al and Jensen et a/.10 11 proposed independently that steroid hormone receptors in the cytoplasm bind incoming steroid molecules and after an "activation" step carry the hormone into the nucleus, where the hormone-receptor complex would bind at many sites in the chromatin inducing transcription of selected genes.12 Doubt has been cast on the assumption that the steroid hormone receptors must bind hormone initially in the cytoplasm. However, the role of steroid receptors in regulating transcription is well established (see discussion in Chapter 22, Section E,5 Chapter 28, Section C,6). 

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