The Thyroid Hormones Are Synthesized from Two Connected Tyrosine Molecules That Contain Three or Four Iodine Molecules
The synthesis of thyroid hormone is unusual because a large amount of the active hormone is stored as a colloid outside the follicle cells, within the lumen (or acinus) created by the circular arrangement of glandular cells.
Two molecules are important for thyroid hormone synthesis: tyrosine and iodine. Tyrosine is a part of a large molecule (molecular weight, 660,000 D) called thyroglobulin that is formed within the follicle cell and secreted into the lumen of the follicle. Iodine is converted to iodide in the intestinal tract and then is transported to the thyroid, where the follicle cells effectively trap the iodide through an active transport process. This allows intracellular iodide concentrations to be 25 to 200 times higher than extracellular concentrations.As iodide passes through the apical wall of the cell, it attaches to the ring structures of the tyrosine molecules, which are part of the thyroglobulin amino acid sequence. The tyrosyl ring can accommodate two iodide molecules; if one iodide molecule attaches, it is called monoiodotyrosine, and if two attach, it is called diiodotyrosine. The coupling of two iodinated tyrosine molecules results in the formation of the main thyroid hormones; two di iodotyrosine molecules form tetraiodothyronine, or thyronine (T4), and one monoiodotyrosine and one diiodotyrosine molecule form triiodothyronine (T3) (Figure 34-2). A key enzyme in the biosynthesis of thyroid hormones is thyroperoxidase (which works in concert with an oxidant, hydrogen peroxide). Thyroperoxidase catalyzes the iodination of the tyrosyl residues of thyroxine-binding globulin (TBG) and the formation of T3 and T4. In addition to the unusual molecular storage form of the hormone, thyroid hormones are also unique in that they are the only hormones that contain a halide (i.e., iodine).