Biochemistry of Thyroid Flashcards
What is the main physiological role of thyroid hormone?
To regulate cellular metabolism and energy homeostasis
What is the secretory unit of the thyroid? Where is thyroid hormone produced?
Thyroid follicle
What are the cells that surround the colloid called? What is the side of the cells that face the colloid called?
Thyroid follicular cells
Apical side
What comprises colloid?
Thyroglobulin
What are the two sides of the thyroid follicle cells?
Apical and basolateral sides
What side of the follicular cells is exposed to the bloodstream?
Basolateral side
What are the two biologically active thyroid hormones?
Thyroxine (T4)
3,5,3’-triiodothyronine (T3)
What is the basic structure of T3 and T4?
A tyrosine molecule linked to a phenyl ring
How many phenyl rings are in T3 and T4?
Two
T3 has two iodine
atoms on its (phenyl or tyrosine) ring.
Tyrosine
What is the significance of removal of an iodine molecule from the tyrosine ring of T3?
Becomes 3,3,5’ triiodothyronine, (reverse T3, rT3) and has NO biological activity
Where does the synthesis of T3 and T4 occur?
T4 is solely in the thyroid gland, whereas T3 can occur in other tissues
Why is it that T3 can be synthesized in many tissues, but T4 can only be synthesized in the thyroid?
T3 is generated by deiodination of T4
What is the major secretion of the thyroid gland: T3 or T4?
T4
Where in the thyroid does the biosynthesis of T3 and T4 occur?
On the surface of thyroglobulin
Where, besides fortified salt, does iodine come from the diet?
seafood
Plants
What is organification?
The process of iodine attachment to the thyroglobulin molecule
What is coupling? What is the enzyme that catalyzes this process?
The synthesis of MITs and DITs together to form T3/T4
TPO
What is the transporter that bring in iodine to the follicular lumen? Where is the transporter located?
Na/I symporter
Basolateral membrane
What does the Na/I symporter do? Is this active or passive?
Brings in one I for every two Na
Secondarily active–relies on Na/K ATPase the constant pumps Na out of the cytoplasm
What happens to the iodide once it enters the cell cytoplasm?
transported to the apical side of the cell, where it is transported by a membrane iodide channel protein
What is the iodide channel protein on the apical side of thyroid cells called? What happens to the iodide once it is transported into the colloid through this protein?
Pendrin
Goes into exocytotic vesicles fused with the apical cell membrane
Where does the organification of iodide occur?
In the exocytotic vesicles
What type of bond is the Iodine to tyrosine bond?
Covalent
What is the enzyme that catalyzes the bond between iodine and thyroglobulin? Where is this found? What is the electrophile for this reaction?
Thyroid peroxidase
It is an integral protein of the apical membrane of follicular cells
H2O2
What percent of tyrosyl residues of thyroglobulin are iodinated?
20-30%
What is the ratio of T4:T3 coupling?
5-7 : 1
What are the steps of thyroglobulin secretion?
Thyroglobulin is endocytosed, and then fuse with cell lysosomes forming phagolysosomes.
There, thyroglobulin is cleaved (hydrolyzed) to release T4 and
T3 but also DIT, and MIT.
They are then secreted.
Where does the conversion of thyroglobulin to T3/T4 take place?
In the phagolysosomes of the colloid
What happens to the MITs and DITs that are hydrolyzed off of thyroglobulin in the lysosome?
Deiodinated by a spseicifc deiodinase, and the iodide is transported back to the apical side of the follicular cells
What happens to the thyroglobulin molecule when the iodines are taken off in the lysosome?
most sent back, but some undergo transcytosis, and are excreted
What does an increase in serum thyroglobulin levels in indicate?
Thyroid pathology
What are the steps involved in the secretion of T3/T4 in terms of the HPA axis?
TRH from the hypothalamus signals the pituitary to release TSH. TSH acts on the thyroid to increase T3/T4 output.
What type of hormone is TRH? What are the components of this?
Peptide hormone
Pyroglutamyl-histidyl-proline residues
What is the precursor to TRH? How does this become TRH? Where does this occur?
proTRH peptide, which undergoes cleavage by the action of peptidases
and cyclization of glutamine
Paraventricular nucleus of the hypothalamus
How does TRH get to the anterior pituitary?
Portal circulation