Biochem: Thyroid Flashcards
Name the two tyrosine derived precursors to the thyroid hormones.
3-Monoiodotyrosine (MIT)
3,5-Diiodotyrosine (DIT)
How does iodide trapping in the thyroid follicular cells work?
A Na+/K+ ATPase on the basal side provides a sodium ion concentration gradient favoring transport into the follicular cells. A Na+/I- symporter (NIS) brings both ions into the follicular cell down the sodium ion gradient.
What is the thyroid colloid?
Colloid is located in the thyroid follicles. It is composed mainly of the glycoprotein thyroglobulin. Thyroglobulin is synthesized in the ER of the follicular cells in the thyroid and then secreted into the follicle. Each follicle is surrounded by follicular cells and is considered extracellular space even though it is completely contained within the thyroid.
Name the apical transporter that moves the iodide ion from the cytoplasm of the follicular cell, into the follicle.
Pendrin
What is the purpose of transporting iodide ions into the thyroid follicles?
Iodide ions are needed to bind to the thyroglobulin proteins to make polymers of Thyroid Hormone (TH).
How is iodine added to the Thyroglobulin?
Use of the Enzyme Thyroid Peroxidase (TPO)
1. Converts iodide ions to iodine
2. Adds iodine to the thyroglobulin side chains forming MIT and DIT
3. Randomly conjugates the MIT and DIT side chains to form Thyroxine (T4) and Triiodothyronine (T3).
(keep in mind the T3 and T4 hormones are still part of the thyroglobulin glycoprotein)
Name the drug class that can inhibit TPO.
Thiocarbamides (ex. Propylthiouracil)
How are the newly formed T3 and T4 hormones transported from the follicle into the follicular cell?
TSH binds to TSH-R on follicular cells. This acts thru a Gs mechanism with a rise in cAMP levels. The rise in cAMP levels induces a change in the actin of the follicular cells. The actin forms pseudopod projections into the colloid and endocytosis the Thyroglobulin proteins that is made up of the formed T4 and T3 hormones.
(TSH also increases expression of NIS, TPO, and thyroglobulin production. Also stimulates glucose production to run the Na/K pump.)
How are T3 and T4 released into circulation from the thyroid follicular cell?
After being endocytosed, the vesicle containing the thyroglobulin immediately fuses with lysosomes. Proteases in the endolysosome remove the T3 and T4 units from the rest of the glycoprotein and are exocytosed into the circulation.
What happens to the thyroglobulin components that are not released into circulation?
Not all the iodinated tyrosine residues are released into circulation. The remaining glycoproteins and iodinated tyrosines come into contact with deiodinase enzymes in the follicular cell cytoplasm and the free iodine and glycoprotein units are recycled.
Name the 3 proteins that aid in TH transport thru the circulation.
- Thyroxine-binding globulin (TBG)
- Transthyretin (TBPA)
- Albumin
Describe the function and location of the Type 1 Deiodinase Enzyme.
Binds T4 and turns it into T3. This is because T3 is much more biologically active. Maintains levels of T3 in the circulation
Located in the liver, kidney, skeletal muscle, thyroid.
Describe the function and location of the Type 2 Deiodinase Enzyme.
Binds T4 and turns it into T3. Maintains T3 levels in brain and pituitary cells.
Describe the function and location of the Type 3 Deiodinase Enzyme.
Inactivates T4 and T3 in the placenta and glial cells of the CNS
Main two functions of Thyrotropin Releasing Hormone (TRH).
Binds thyrotropes and lactotropes in the anterior pituitary and signals TSH and PRL production and release.
