Thyroid hormone synthesis

Thyroid Factor

The Natural Thyroid Diet

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This involves the following steps:

* Dietary iodine is largely converted to iodide in the gut and absorbed into the circulation. The main sources of dietary iodine are iodised salt, iodated bread and dairy products. Iodine is also present in medications, disinfectants and radiographic contrast media.

* Iodide trapping by the thyroid gland (iodide pump in the basolateral membranes of the follicular epithelial cells: sodium-iodide co-transport-symport)

is an active transport mechanism, stimulated by TSH. The TSH receptor on h g the basolateral membrane surface is a G-protein-coupled receptor. The iodide 5

d carrier is a 643 amino acid transport protein with 13 transmembrane domains, known as the sodium iodide symporter. The concentration of free iodide achieved is around 30 to 40 times that in plasma.

* Iodide oxidation to free iodine (peroxidase-H2O2 system). Thyroid peroxidase is a membrane-bound glycoprotein with a molecular weight of 102 000 and a hame compound as the prosthetic group. It is synthesised in the rough endoplasmic reticulum.

* Thyreoglobulin synthesis by the endoplasmic reticulum of the thyroid cells. Thyroglobulin is a homo-dimeric glycoprotein with 5496 amino acids and a molecular weight of 660 000. The glycosylation of thyroglobulin is completed in the Golgi apparatus prior to secretion into the colloid of the follicular lumen.

* Iodination of tyrosine residues in thyroglobulin to give monoiodotyrosine (MIT) and diiodotyrosine (DIT).

* Coupling of the iodotyrosines to give iodothyronines: MIT + DIT = triiodothyrosine (T3); DIT + DIT = thyroxine (T4). The iodination and subsequent coupling reactions are catalysed by thyroid peroxidase.

* The synthesis of thyroid hormone occurs at the apical membranes of the follicular epithelial cells.

* Storage takes place extracellularly in the colloid of the thyroid follicles.

* Secretion of thyroid hormones follows proteolysis of thyroglobulin within endocytotic vesicles by endosomal and lysosomal enzymes. Proteolysis is initiated by cathepsins D, B and L. Exopeptidases release free T3 and T4. The thyroid predominantly produces T4, which is converted in peripheral tissues to the metabolically active form T3.

* The iodotyrosines MIT and DIT are deiodinated by an iodotyrosine deiodinase and their iodide re-enters the intra-thyroidal pool where it is recycled.

The control of thyroid hormone secretion and action occurs at three levels: The hypothalamic-pituitary-thyroid axis;

Autoregulation within the thyroid depending on organic iodine content; Peripheral hormone conversion.

Increasing iodide intake may occasionally either reduce total organic iodine (Wolf-Chaikoff effect) or increase organic iodine, especially in iodine deficiency areas (Jod-Basedowphenomenon).

Iodothyronines in the circulation are bound to thyroxine-binding globulin (70% of T4 and 80% ofT3), albumin (20% ofT4 and 10% ofT3) and transthyretin (10% of T4 and 10% ofT3). Only about 0.03% ofT4and0.3% ofT3 is free in the circulation.

Characteristics of the iodide pump e Located in the basal plasma membrane of follicular cells;

h Concentrates iodide against chemical and electrical gradient;

y i Saturable and obeys Michaelis-Menten kinetics;

o Depends on ATP availability (derived from oxidative phosphorylation or glycolysis);

"< Concentrates other monovalent anions;

Inhibited by anions (bromide, perchlorate, pertechnetate, thiocyanate) and Na+-K+ activated; ATPase inhibitors (ouabain).

Tyrosine + iodine

Monoiodotyrosine

Diiodotyrosine

T3 T4

Figure 10.3 Pathway for thyroid hormone synthesis

The half-life of T4 is from 5 to 7 days, and that of T3 is from 1 to 3 days.

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