How is thyroxine synthesized from its inactive precursor, in short, its activation pathway?

Answer 1

Thyroxine (T4) synthesis occurs in the thyroid gland through the following steps:

1. Iodide uptake: Sodium-iodide symporter (NIS) transports iodide from the bloodstream into thyroid follicular cells.

2. Iodine oxidation: Thyroperoxidase enzyme (TPO) oxidizes iodide to iodine, which is now ready to be added to tyrosine residues in thyroglobulin.

3. Thyroglobulin iodination: TPO attaches iodine to tyrosine residues in thyroglobulin, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT).

4. Thyroglobulin coupling: TPO catalyzes the coupling of one MIT and one DIT to form triiodothyronine (T3), or two DITs to form thyroxine (T4). These hormones remain bound to thyroglobulin, stored as colloid within the follicles.

5. Endocytosis and proteolysis: When thyroid hormones are needed, thyroglobulin-bound T4 and T3 are endocytosed into follicular cells. Proteases then cleave thyroglobulin, releasing free T4 and T3.

6. Secretion: T4 and T3 are transported across the basolateral membrane of the follicular cells by the monocarboxylate transporter (MCT) system, and subsequently released into the bloodstream.

Note that T4 is the primary hormone secreted by the thyroid gland, and peripheral tissues convert T4 into the more active T3 via deiodination by specific enzymes (deiodinases).