Triiodothyronine addition

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]. 

The amino acid tyrosine is the starting point in the synthesis of the catecholamines and of the thyroid hormones tetraiodothyronine (thyroxine T4) and triiodothyronine (T3) (Figure 42-2). T3 and T4 are unique in that they require the addition of iodine (as T) for bioactivity. Because dietary iodine is very scarce in many parts of the world, an intricate mechanism for accumulating and retaining T has evolved. 

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. 

Thioamides are reducing agents. They inhibit thyroid hormone synthesis by inhibiting the peroxidase enzymatic system, which catalyzes oxidation of iodide ions and iodine that are consumed in food, which is necessary for iodination of tyrosine derivatives. Thus they reduce the concentration of free iodine necessary to react with tyrosine derivatives, and they can also block oxidative addition reactions of mono- and diiodtyrosines, which form L-thyroxine and L-triiodothyronin. 

A prominent advantage of this assay procedure is the feature that the complex of hapten and labeled antibody was captured on a solid phase (PMP) and separated from the reaction medium before signal determination. This additional step not only reduces interference due to biological specimens but also eliminates the tedious transfer of supernatant, which is essential in conventional immunometric assays. This immunometric assay provided somewhat improved specificity in terms of the cross-reactivities with T2 and reverse T3 (3,3, 5 -L-triiodothyronine). The authors speculated that the dissociation rate of the antibody-cross-reactant complex would be faster than that of an antibody-analyte complex thus the former binding would be preferentially substimted by T2 immobilized on CPG. 

A common mistake is to treat bipolar depression in the same manner that one treats unipolar depression, overlooking the need for a mood stabilizer. In bipolar depression, the first pharmacological intervention should be to start or optimize treatment with a mood stabilizer rather than to start administering an antidepressant medication. In addition, thyroid function should be evaluated, particularly if the patient is taking lithium. Subclinical hypothyroidism, manifested as an increased thyroid-stimulating hormone level and normal triiodothyronine and thyroxine levels, may present as depression in affectively predisposed individuals. In such cases, the addition of thyroid hormones may be beneficial, even if there is no other evidence of hypothyroidism. 

Three types of iodothyronine deiodinase remove iodine atoms from thyroxine to form the active thyroid hormone triiodothyronine and also to inactivate the hormone by removing additional iodine531 541-546 (see also Chapter 25). In this case the - CH2- Se- may attach the iodine atom, removing it as I+ to form -CH2-Se-I. The process could be assisted by the phenolic -OH group if it were first tautomerized (Eq. 15-60). 

Sodium and potassium iodides find limited use as expectorants but a much more important use is as additives, at levels around 5—100 fig/g to table salt in many countries as a prophylactic against goitre. This is a condition arising from iodine deficiency with the result that there is insufficient synthesis of the iodine-containing amino acids, thyroxine and 3,3, 5-triiodothyronine, that are essential components of the... 

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... 

In addition to its function in thiol/disulfide exchange, Grx-1 also serves as an alternative electron donor to ribonucleotide reductase (Fernandes and Holmgren 2004), participates in deiodination of thyroxine to triiodothyronine (Takagi et al. 1989), and acts as a dehydroascorbate reductase for regenerating ascorbic acid (Washburn and Wells 1989). However, despite the potential role of Grx in... 

Q2 Thyroxine (T4), the major hormone secreted together with triiodothyronine (T3). T3 is more active metabolically than T4. In addition the hormone calcitonin is secreted by the medullary cells of the thyroid gland. 

Iodine is a powerful oxidizing agent and has a direct action on cells by precipitating proteins. The affected cells may be destroyed. In addition to the primary irritant action of iodine, this compound can act as a potent sensitizer. Iodine is an integral part of thyroid hormones (tetraiodothyronine (thyroxine) and triiodothyronine), and deficiency results in compensatory hyperplasia and hypertrophy of the thyroid gland (endemic goiter). Endemic goiter occurs naturally where soil is deficient in iodine. 

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. 

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