In thyroid hormone synthesis

The final step in thyroid hormone synthesis is the coupling of two iodotyrosines within a single peptide chain of Tg to form the iodothyronine T4 or T3. Both the coupling of two DITs to form T4 and the coupling of a MIT with a DIT to form T3 are catalyzed by the enzyme TPO. 

The thyroid gland is made up of multiple follicles that consist of a single layer of epithelial cells surrounding a lumen filled with colloid (thyroglobulin), the storage form of thyroid hormone. A diagram of the steps in thyroid hormone synthesis and secretion is shown in Figure 25.6. 

The third step in thyroid hormone synthesis is cleavage of the aromatic R group from one of the iodinated tyrosines in the dimer. As a result, one of the iodotyros-... 

The second step in thyroid hormone synthesis is the covalent bridging of two different residues of iodinated tyrosine. A dimer is formed, reminiscent of the dimers of cysteine in proteins (the cysteine dimer is called cystine). Only a small fraction of the iodinated tyrosines is bridged in this way. More specifically, only four of the iodinated tyrosines, located at positions 5,2555,2569, and 2748, participate in the reaction. The numbers refer to the amino acid, cormting from the amino terminus of the protein. Thyroglobulin has 2748 amino acids. The first and second steps are catalyzed by thyroperoxidase, a heme protein. It requires hydrogen peroxide for activity. To summarize, thyroperoxidase catalyzes the attachment of iodine atoms to residues of tyrosine as well as the subsequent cross-linking of the iodinated tyrosine residues. 

The steps in thyroid hormone synthesis and the antithyroid agents effects upon them are summarized in Table VII-2-2. The clinical uses and their potential complications are presented in greater detail for the thioamides (propylthiouracil and methimazole) and iodine. 

Iodide interferes with the TSH system as the fimit-ing factor in thyroid hormone synthesis. In iodine deficiency, low thyroid hormone synthesis and secretion lead to increased TSH secretion and thyroid stimulation. 

It has also been mentioned that salt iodization efficacy, the preferred strategy for IDD, might be influenced by ID, because this disorder impairs thyroid metabolism (WHO, 2001, Zimmermann et al., 2000). It has been observed that two initial steps in thyroid hormone synthesis are catalyzed by Fe-dependent thyroid peroxidase (TPO). One Fe-defl-ciency anemia study in rats showed reduced TPO activity, and decreased plasma T4 and triiodothyronine (T3) levels (Hess et al, 2002). IDA may also alter the central nervous systems thyroid metabolism control, and reduce T4 to T3 peripheral conversion (Beard etal, 1998), modify nuclear T3 binding (Smith et al, 1994), and increase circulating thyrotropin (TSH) (Beard et at, 1990). The therapeutic response to oral iodized oil is impaired in children with IDA compared with Fe-sufficient children (Zimmermann et al, 2000). 

Ageing is accompanied by a decrease in iodine uptake by the thyroid gland, and a reduction in thyroid hormone synthesis and release. There is a decrease in the rate of production of thyroxine (T4) in the thyroid gland, and a decrease in triiodothyronine (T3) production, due to a decreased conversion rate of T4 to T3 by 5 -monodeiodi-nase in the peripheral tissues (Mariotti et ai, 1995). 

The reasons for briefly discussing PBI techniques in this review are minimal except for the fact that many automated units are still operating and because a PBI determination is sometimes useful in conjunction with other tests in delineating the site of a biosynthetic block in thyroid hormone synthesis. The subject was last reviewed in the series Advances in Clinical Chemistry by Chaney (C6) in 1958, and probably the most recent review is by Acland in 1971 (A4). 

Each of these steps in thyroid hormone synthesis will be considered separately, and evidence on the nature of the circulating thyroid hormone will be presented. 

S. Nagataki and S. H. Ingbar. Relation between qualitative and quantitative alterations in thyroid hormone synthesis induced by varying doses of iodide. Endocrinology. 74 731(1964)... 

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