step of thyroid hormone synthesis
1. Iodide trapping: The first step in thyroid hormone synthesis is the transport of iodide ions into the thyroid follicular cells. This is mediated by an iodide transporter, known as the sodium iodide symporter (NIS), which actively transports iodide from the blood into the follicular cells.
2. Thyroglobulin synthesis: Thyroglobulin (TG) is a large glycoprotein that is synthesized within the follicular cells. It serves as a scaffold for thyroid hormone synthesis and storage. The synthesis of TG occurs in the endoplasmic reticulum of the follicular cells.
3. Iodination of tyrosine residues: Within the colloid-filled follicular lumen, iodide ions are oxidized to iodine, facilitated by an enzyme called thyroid peroxidase (TPO). The iodine atoms are then covalently attached to tyrosine residues on TG, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT).
4. Coupling of iodotyrosines: MIT and DIT residues on TG can undergo an enzyme-mediated reaction to form either T3 (triiodothyronine) or T4 (thyroxine). One MIT and one DIT residue combine to form T3, while two DIT residues combine to form T4.
5. Endocytosis and proteolysis: Once sufficient amounts of T3 and T4 are synthesized, the thyroid follicular cells engulf the colloid via endocytosis. The TG-filled vesicles then fuse with lysosomes, where proteases break down TG to release T3 and T4.
6. Secretion of thyroid hormones: T3 and T4 are transported out of the follicular cells and into the bloodstream. They bind to carrier proteins, such as thyroxine-binding globulin (TBG), which assist in their transport to target tissues throughout the body.
7. Peripheral activation of T4: Once in the target tissues, T4 can be enzymatically converted to T3 by the removal of one iodine atom. This conversion primarily occurs in the liver and kidneys and is facilitated by the enzyme deiodinase.
These steps collectively contribute to the synthesis, storage, release, and activation of thyroid hormones within the body.
The synthesis of thyroid hormones is a complex process that involves several steps. Here is an overview of the steps involved in thyroid hormone synthesis:
1. Uptake of iodide: Iodide, an essential component for thyroid hormone synthesis, is taken up from the bloodstream into the thyroid follicular cells. This process is facilitated by the sodium/iodide symporter (NIS) located in the cell membrane.
2. Oxidation of iodide: Once inside the thyroid follicular cells, iodide is converted to iodine by an enzyme called thyroid peroxidase (TPO). This step is crucial for incorporating iodine into the thyroid hormone molecules.
3. Organification of iodine: Iodine is then attached to tyrosine residues within a protein called thyroglobulin (Tg), creating monoiodotyrosine (MIT) and diiodotyrosine (DIT) molecules. This reaction, also catalyzed by TPO, occurs within the colloid-filled follicles of the thyroid gland.
4. Coupling of MIT and DIT: MIT and DIT molecules are then coupled together to form the active thyroid hormone molecules, known as triiodothyronine (T3) and thyroxine (T4). T3 contains three iodine atoms, while T4 contains four. This process occurs within the thyroglobulin protein.
5. Thyroglobulin endocytosis and breakdown: Thyroglobulin, containing T3 and T4, is internalized by the follicular cells through endocytosis. Within the follicular cells, lysosomal enzymes degrade thyroglobulin, releasing T3 and T4 into the circulation.
6. Thyroid hormone release: T3 and T4 are then released into the bloodstream, where they bind to transport proteins to be distributed throughout the body. The majority of thyroid hormones are bound to proteins like thyroxine-binding globulin (TBG), while a smaller fraction remains unbound, or "free."
It's important to note that the regulation of this process is complex and involves various factors, including the pituitary gland's secretion of thyroid-stimulating hormone (TSH) and feedback loops that maintain hormonal balance in the body.
The synthesis of thyroid hormones primarily takes place in the thyroid gland. Here are the steps involved in thyroid hormone synthesis:
1. Iodide uptake: The first step is the active transport of iodide ions (I-) from the bloodstream into the thyroid gland. This process is facilitated by a protein called the sodium-iodide symporter (NIS) located on the surface of thyroid follicular cells.
2. Oxidation and organification: Once inside the follicular cells, iodide ions are actively transported into the thyroid follicles. Here, they are oxidized by an enzyme called thyroid peroxidase (TPO) to form iodine (I2). This iodine is then organified, meaning it binds to a protein called thyroglobulin (Tg), which is produced by the follicular cells.
3. Thyroglobulin synthesis: Thyroglobulin, a large glycoprotein, is synthesized within the follicular cells and then secreted into the colloid space of the thyroid follicles. It consists of two identical subunits, each containing multiple tyrosine residues.
4. Iodination of tyrosine residues: Within the colloid space, iodine atoms are added to specific tyrosine residues on the thyroglobulin molecule. This process is catalyzed by TPO. One or two iodine atoms can be added to each tyrosine residue, resulting in the formation of monoiodotyrosine (MIT) or diiodotyrosine (DIT), respectively.
5. Coupling of MIT and DIT: MIT and DIT residues on the thyroglobulin molecule can combine to form thyroxine (T4). This occurs when one MIT combines with one DIT, resulting in the formation of a T4 molecule. Alternatively, two DITs can combine to form triiodothyronine (T3), a less abundant but more biologically active thyroid hormone.
6. Endocytosis and digestion of thyroglobulin: Once the coupling of iodinated tyrosine residues is complete, the thyroglobulin molecules with T4 and T3 attached are engulfed by the follicular cells through endocytosis. The vesicles containing thyroglobulin are then fused with lysosomes, allowing the digestive enzymes to break down the protein and release free T4 and T3.
7. Release of thyroid hormones: The free T4 and T3 produced by the digestion of thyroglobulin are released into the bloodstream, where they can travel to target tissues throughout the body. The majority of thyroid hormones are transported bound to carrier proteins such as thyroxine-binding globulin (TBG), which helps regulate their distribution and metabolism.
It is important to note that this is a simplified overview of the steps involved in thyroid hormone synthesis. The regulation of these processes is complex and involves various control mechanisms to maintain the balance of thyroid hormone levels in the body.