3,5,3 - Triiodothyronine metabolism

The thyroid gland, located in the base of the neck, exerts i key role on growth and metabolism. In contrast with that of some of the other endocrine glands, this control is effected Ihrough a pair of relatively simple molecules, thyroxine, and its close congener, triiodothyronine. Cases of thyroid deficien-cy (hypothyroidism) are common enough to warrant the production... 

Thyroid gland. An endocrine gland that secretes thyroxin and triiodothyronine, hormones that modulate the rate of cellular metabolism. 

Propylthiouracil (PTU), but not methyl-mercaptoi-midazole (MMI), has an additional peripheral effect. It inhibits the monodeiodination of thyroxine to triiodothyronine by blocking the enzyme 5 mono-deiodinase [1]. In humans the potency of MMI is at least 10 times higher than that of PTU, whereas in rats PTU is more potent than MMI. The higher potency of MMI in humans is probably due to differences in uptake into the thyroid gland and subsequent metabolism, because in vitro inhibition of thyroid peroxidase by MMI is not significantly more potent than by PTU [1, 6]. Whether antithyroid drags have additional immunosuppressive actions is a matter of discussion [1, 2]. 

Triiodothyronine (3, 5,3-L-triiodothyronine, T3) is a thyroid hormone. It is producedby outer ring deiodination of thyroxine (T4) in peripheral tissues. The biologic activity of T3 is 3-8 times higher than that of T4. T3 is 99.7% protein-bound and is effective in its free non-protein-bound form. The half-life of triiodothyronine is about 19 h. The daily tur nover of T3 is 75%. Triiodothyronine acts via nuclear receptor binding with subsequent induction of protein synthesis. Effects of thyroid hormones are apparent in almost all organ systems. They include effects on the basal metabolic rate and the metabolisms of proteins, lipids and carbohydrates. 

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.

The gland is situated in the neck across the front of the trachea. It secretes thyroxine (T4), which is converted to the active form of the hormone, triiodothyronine (T3), in peripheral tissues. It stimulates metabolic activity in tissues so that it increases heat production (for example, by stimulating protein turnover and substrate cycles). 

The amino acids that are made available as a result of protein degradation in starvation are nsed as precursors of glucose, which is required for the brain. The decline in starvation-induced protein degradation is a result of the decreased requirement for glucose by the brain due to the increase in utilisation of ketone bodies. The qnestion arises, therefore, as to the mechanism by which the protein breakdown in muscle is reduced. Two answers, which are interdependent, have been put forward (i) decreased metabolic activity in tissues, and (ii) a decrease in the plasma level of thyroxine and hence triiodothyronine. 

Produces tyroxine and triiodothyronine hormones Adrenals Stress response, blood pressure, glucose metabolism, salt and water balance... 

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. 

Z)-2,3-Methanothyronine 59 and its dibromo derivative 60 have comparable activity with the thyroxine 61, a thyroid hormone [66], which exhibited thyro-mimetic activities in basal metabolism and antigoiter tests (comparison of oxygen consumption and heart rate in normal and thyroidectomized rats) but did not have an inhibitory action on the metabolism developed by triiodothyronine [66]. (Z)-2,3-Methanohistidine 62, tested on rat liver, is an effective inhibitor of histidine decarboxylase, Eq. (23) [67]. 

Sulfotransferases (SULTs) are important for the metabolism of a number of drugs, neurotransmitters, and hormones, especially the steroid hormones. The cosubstrate for these reactions is 3 -phosphoadenosine 5 -phosphosulfate (PAPS) (Fig. 4.1). Like the aforementioned enzymes, sulfate conjugation typically renders the compound inactive and more water soluble. However, this process can also result in the activation of certain compounds, such as the antihypertensive minoxidil and several of the steroid hormones. Seven SULT isoforms identified in humans, including SULTs lAl to 1A3, possess activity toward phenolic substrates such as dopamine, estradiol, and acetaminophen. SULTIBI possesses activity toward such endogenous substrates as dopamine and triiodothyronine. SULTIEI has substantial activity toward steroid hormones, especially estradiol and dehydroepiandrosterone, and toward the anti-... 

An understanding of absorption, binding, metabolism, and excretion is more important for phenytoin than it is for most drugs. Following oral administration, phenytoin absorption is slow but usually complete, and it occurs primarily in the duodenum. Phenytoin is highly bound (about 90%) to plasma proteins, primarily plasma albumin. Since several other substances can also bind to albumin, phenytoin administration can displace (and be displaced by) such agents as thyroxine, triiodothyronine, valproic acid, sulfafurazole, and salicylic acid. 

Mechanism of Action A synthetic form of triiodothyronine (T3), a thyroid hormone involved in normal metabolism, growth, and development. Possesses catabolic and anabolic effects. Therapeutic Effect Increases basal metabolic rate, enhances gluco-neogenesis, and stimulates protein synthesis. 

Lithium blocks the release of thyroxine (T4) and triiodothyronine (T3) mediated by thyrotropin (Kleiner et ah, 1999). This results in a decrease in circulating T4 and T3 concentrations and a feedback increase in serum thyrotropin concentration. It also inhibits thyrotropin-stimulated adenylate cyclase activity (Kleiner et ah, 1999). Lithium has varying effects on carbohydrate metabolism. Increased and decreased glucose tolerance and decreased sensitivity to insulin have been observed (Van derVelde Gordon, 1969). In animals, lithium decreases hepatic cholesterol and fatty acid synthesis. 

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 normal thyroid gland secretes sufficient amounts of the thyroid hormones—triiodothyronine (T3) and tetraiodothyronine (T4, thyroxine)—to normalize growth and development, body temperature, and energy levels. These hormones contain 59% and 65% (respectively) of iodine as an essential part of the molecule. Calcitonin, the second type of thyroid hormone, is important in the regulation of calcium metabolism and is discussed in Chapter 42. 

An important product of tyrosine metabolism in vetebrates is the thyroid hormone101 of which the principal and most active forms are thyroxine (T4) and triiodothyronine (T3).102 The thyroid gland is rich in iodide ion, which is actively concentrated from the plasma to 1 pM free I. 103 This iodide reacts under the influence of a peroxidase (see Fig. 16-14 and accompanying discussion)104 to iodinate tyrosyl residues of the very large 660-kDa dimeric thyroglobulin, which is stored in large amounts in the lumen of the... 

Thyroxine and triiodothyronine have many effects, a major one in mammals and birds being stimulation of energy metabolism in tissues. It has long been recognized that a deficiency of thyroid hormone is reflected in an overall lower basal metabolic rate (Chapter 6). Maley and Lardy observed that thyroxine uncouples oxidative phosphorylation (Chapter 18) in isolated mitochondria.117 When mitochondria from animals receiving extra thyroxine were compared with those from control animals, an increased rate of electron transport was observed. However, there was little or no change in the P / O ratio. Thus, the hormone apparently increased the rate of electron transport... 

Burger A, Dinichert D, Nicod P, Jenny M, Lemarchand-Beraud T, Vallotton MB. Effect of amiodarone on serum triiodothyronine, reverse triiodothyronine, thyroxin, and thyrotropin. A drug influencing peripheral metabolism of thyroid hormones. J Clin Invest 1976 58(2) 255-9. 

There was a modest rise in serum TSH concentration when rifampicin was given to a patient previously stabilized on thyroxine replacement (87). Rifampicin is believed to increase the metabolic clearance of both thyroxine and the inactive compound reverse triiodothyronine and in healthy volunteers it reduces circulating concentrations of total and free thyroxine, although in subjects without thyroid disease it has no effect on serum TSH (86). 

Fish LH, Schwartz HL, Cavanaugh J, Steffes MW, Bantle JP, Oppenheimer JH. Replacement dose, metabolism, and bioavailability of levothyroxine in the treatment of hypothyroidism. Role of triiodothyronine in pituitary feedback in humans. N Engl J Med 1987 316(13) 764-70. 

The active T-4 circulating in the vascular system merges with receptors and triggers metabolic activity but when it reaches the liver it is changed into the more active thyroid hormone L-Triiodothyronine (T-3) by an enzyme called 5-deiodinase. T-3 is about 5 times more active than T-4. The newly formed T-3 is released into the vascular system where it may contact and merge with cellular receptors which initiates all the metabolic activity discussed earlier. 

An advantage of T-3/L-triiodothyronine administration over T-4/L-thyroxine was the lack of dependence upon the liver enzyme responsible for T-4/T-3 conversion. During diet restricted periods the liver naturally decreases the liver enzyme levels as a control measure to prevent metabolic rate induced starvation. Just as the liver increases production of this enzyme in response to elevated calorie intake it also reduces levels in response to decreased calorie intake. Remember that T-4 /L-thyroxine is only 20% as active as T-3/L-triiodothyronine. 

Triacana is a trade or brand name for the thyroid drug Tiratricol. The body naturally (endogenously) produces T-4/L-thyroxine, T-3/L-triiodothyronine, and T-2 /L-diiodothyronine. Triacana is simply a synthetic form of these three thyroid hormones natural metabolite product, Triiodothyroacetic acid, or tiratricol for short. This means the body naturally produces Triacana as a metabolic by-product of other thyroid hormones. 

Thyroid Thyroxine (T4], Triiodothyronine (T3] Increase cellular metabolism facilitate normal growth and development... 

Because thyroxine contains four iodine residues, this compound is also referred to by the abbreviation T4. Likewise, triiodothyronine contains three iodine residues, hence the abbreviation T3. There has been considerable discussion about which hormone exerts the primary physiologic effects. Plasma levels of T4 are much higher than T3 levels, but T3 may exert most of the physiologic effects on various tissues, which suggests that T4 is a precursor to T3 and that the conversion of T4 to T3 occurs in peripheral tissues.23 Regardless of which hormone ultimately affects cellular metabolism, both T4 and T3 are needed for normal thyroid function. 

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