Lecture 22 Flashcards
(31 cards)
Where do thyroid hormones act in the body? What are the function of thyroid hormone?
Thyroid hormone act on nearly every cell in the body.
Functions:
- increase BMR
- cause heat generation
- affect protein synthesis
- regulate protein, fat, and carbohydrate metabolism
- helps regulate long bone growth (can cause short stature if you don’t have enough)
- neural maturation
- increase body’s sensitivity to catecholamines (adrenaline/noradrenaline)
The two lobes of the thyroid are connected by what? Where are the parathyroid glands found in mammals?
Connected by the isthmus. The parathyroid glands lie on the surface of the thyroid gland.
What structures in the throat surrounds the thyroid gland?
- Jugular veins: bring blood back to the heart
- common carotid artery: bring blood to the head/brain
- thyroid cartilage: helps support the thyroid structure
- vagus nerve: both sides of the thyroid
- trachea
The thyroid glands contain parafollicular or C cells secrete what?
Calcitonin
What is the functional unit of the thyroid? What do these functional units do?
The functional unit of the thyroid is the follicle, a single layer of epithelial cell which surround a colloid-filled lumen.
The epithelial cells of the thyroid follicle is the site of iodine transport and the formation and secretion of the thyroid hormones. These follicle cells are the functional cells that help produce these really important hormones.
Know how the draw the structures of tyrosine, monoiodotyrosine, diiodotyrosine, thyronine, T3 and T4 Label the carbons on thyronine. What are the names of T3 and T4?
T3: 3, 5, 3’-triiodothryonine
T4: 3, 5, 3’, 5’-tetraiodothyronine (thyroxine)
What is the T4 form of the thyroid hormone?
storage form
Where do the steps of thyroid hormone synthesis take place? Explain the structures of what synthesized the thyroid hormone.
All steps take place in the thyroglobulin (Tg) which makes up most of the colloid which fills the lumen of the thyroid follicle cell.
Thyroglobulin is composed of two subunits, containing 134 tyrosine residues per monomer. In each monomer are 20-30 tyrosines which are iodinated and 6-8 iodothyroninTes.
The coming together of two diiodotyrosine residues leads to the formation of what thyroid hormone?
The coming together of one diiodotyrosine residue and a monoiodothyronine residue leads to the formation of what thyroid hormone?
2 diiodotyrosine = T4 (thryoxine)
diiodotyrosine + monoiodotyrosine = T3 (triiodothyronine)
Each thyroglobulin protein yields how much thyroid hormone? How many molecules of T4 and T3 are produced by the thyroglobulin proteins?
Only small amounts of thyroid hormone is produced. Each Tg yields 5-6 molecules of T4 or T3 but there are a lot of thyroglobulin proteins which fill the lumen of the thyroid follicles.
What is the major form of thyroid hormone present in the blood? What is the ratio of thyroid hormones released into the blood, and which thyroid hormone is the active/more-potent form?
Major form: T4 (thyroxine)
T4:T3 is between 14:1 to 20:1. However, T4 is converted into active T3, which is 3 to 4 times more potent than T3.
How is T4 converted into T3? Where does this occur?
Thyroxine (T4) is converted into triiodothyronine (T3) within cells by deiodonases. This enzyme will remove the 5’-iodine present on T4, converting it into T3.
Triiodothyronine (t3) affects almost every physiological process in the body like what?
- Growth and development
- metabolism
- body temperature
- heart rate
Explain the process of thyroid hormone synthesis, storage, and secretion - all beginning from iodide obtained from your diet, not present in your blood.
1) Iodide from diet enters endothelial cells lining the lumen of the thyroid follicle through Na+/I- symporters which form concentration gradients that allow 2 sodium to enter the cell and allowing 1 iodide into the cell.
2) Iodide is sent to the lumen/colloid through another transporter to be used for iodination.
3) mRNA for thyroglobulin transcribed in the nucleus has been stimulated. The rough ER aids in thyroglobulin mRNA translation into thyroglobulin by ribosomes. Thyroglobulin is then sent from the ER to golgi such that it can be sent into colloid/lumen through vesicles and stored.
4) Thyroglobulin is iodinated at tyrosine residues by thyroid peroxidase after iodide ions are converted into iodide radicals. (iodinated tyrosine residues on the thyroglobulin backbone are either monoiodotyrosine or diiodotyrosine.)
5) MIT and DIT are combined to form T3 and T4 on the backbone of thyroglobulin. Thyroglobulin containing T3 and T4 enters the follicle cells surrounding colloid/lumen through endocytosis and cleaved off from thyroglobulin through proteolysis.
6) T3 and T4 are sent out from thyroid follicular cells through transporter after being cleaved off and sent into the blood to different tissues to thyroid hormone receptors to exert their effects.
What is the concentration of iodide in the thyroid follicular cells with respect to the concentration of iodide in the blood?
Iodide concentrates in the thyroid. There is about 30x the concentration of iodide in the thyroid follicular cells with respect to the concentration of iodide in the blood.
Iodine concentrates in the thyroid. Why can this be problematic, especially after a nuclear explosion?
Iodine concentrating in the thyroid can be problematic after a nuclear explosion because nuclear material can decay into radioactive iodine. The radioactive iodine can concentrate in your thyroid, which can lead to the development of a very specific type of thyroid cancer which affects the parafollicular cells.
Because radioactive iodide concentrates in the thyroid, this can lead to development of thyroid cancer affecting the parafollicular cells.
How is the protein pendrin involved in the pathway for synthesis/storage/secretion of thyroid hormones?
Pendrin is a transporter that is going to be involved in transporting/pushing iodide into the lumen/colloid of the thyroid follicle. This transporter allows thyroid peroxidase (TPO) to have access to iodide, such that iodine radicals can be created, allowing for the formation of the MIT and DIT
What transporter is responsible for the export of T3 and T4 into the bloodstream?
MCT8 (monocarboxylate transport protein 8)
What does the enzyme DEHAL do? What does DEHAL stand for?
DEHAL (dehalogenase) is responsible for removing iodine from diiodotyrosine (DIT) and monoiodotyrosine (MIT) present in the endothelial/thyroid follicle cells.
What molecules act as inhibitors for the uptake of iodine by the thyroid? What enzyme activity does this prevent as a result of inhibition of iodine uptake?
1) Perchlorate and Thiocyanate prevents thyroid peroxide from being able to have substrate (iodine,) such that no radical iodine can be produced, preventing MIT and DIT from being produced and preventing T3 and T4 synthesis from being able to occur.
2) Methimazole will prevent iodide oxidation to the radical iodine (no iodination of tyrosine can occur = prevention of MIT and DIT production)
3) Propylthiouracil will prevent the overall iodination of the thyroglobulin (prevents MIT and DIT production = no T3 or T4 produced)
When thyroglobulin produces the iodinated tyrosines (MIT and DIT) in the lumen/colloid of the thyroid follicle, how much T4 are they able to produce and how long will this storage of T4 be able to last?
5 mg of T4 is produced and lasts about 50 days.
1) Most of the thyroid hormones circulating the blood are bound to what, making them active/inactive? Why?
2) However, a very small fraction of thyroid hormone that circulates is what? Is this the active or inactive biological form of thyroid hormone.
3) Which forms of thyroid hormone are measured through panels as a diagnostic tool, and which form matters the most for measurement?
1) They are bound to transport proteins (like thyroxine-binding globulin), making them inactive. Some hormones tend to be hydrophobic or not be able to circulate in the blood, therefore there is some type of carrier which carried them through the blood.
2) it’s unbound (a free thyroid hormone) which is the active biological form of thyroid hormone.
3) The thyroid hormone that is unbound to any other proteins and thyroid hormone bound to thyroxine-binding globulin is measured. However, the amount of free T3/T4 is what happens most because this is the active form.
Which form of thyroid hormone is used as the reservoir for inactive thyroid hormone in the body? What does this allow our body to be able to do?
T4 is the reservoir for inactive thyroid hormone. As a result, our body is able to obtain T3 through deiodination of T4.
What are the concentrations of T4 and T3 in our serum and in our body pool? What are the half lives of T4 and T3 in our serum?
Concentrations in serum: 8 nmol/L of T4 and 0.12 nmol/L of T3
Concentrations in body pool: 810 nmol T4 and 46 nmol T3
Half lives: 6-7 days for T4 and 1 day for T3
This all indicates that T4 is slowly turned over and is present in much higher amounts of the body whereas T3 is rapidly turned over and is present in much lower amounts in the body.
