EXAM #1: NORMAL BIOCHEMISTRY AND PHYSIOLOGY Flashcards
What is the precursor of the thyroid hormones?
Tyrosine
What is the active form of thyroid hormone? Which is more active?
T3* and T4
*T3 is more active
What are the biologicaly inactive forms of the thyroid hormones?
T2 and rT3
Where are thyroid hormones synthesized?
Thyroid follicle
What direction does the apical side of the follicular cell face? Basal?
Apical= colloid
Basal= bloodstream
What is the platform for T3 and T4 synthesis?
Thryoglobulin
What is exogenous substance is required for the synthesis of thyroid hormones?
Iodine
What has virtually eliminated iodine deficiency in the US?
Iodized salt
How is iodine transported into the thyroid follicle?
Na+-I cotransporter (symporter)
What is organification?
Adding iodine to thyroglobulin
What is the site of organification?
Exocytotic vesicles in the colloid
Outline the process of organification.
Thyroid peroxidase oxidizes and attaches iodide to the tyrosyl residues
*Uses hydrogen peroxide
What is the outcome of organification?
Formation of MIT and DIT
*MIT= 1 iodine DIT= 2x iodine
What is the next step after organification?
Coupling
What enzymes is responsible for coupling?
Thyroid peroxidase (TPO)
How is thyroglobulin released via the lysosomal pathway?
1) Endocytosis
2) Hydrolysis in the lysosome/ proteolysis
3) Diffusion into the circulation
What happens to thyroglobulin after cleavage of T3 and T4 during release?
1) Recycled to colloid
2) Transcytosis into the circulation
Describe the composition of TRH.
Pyroglutamul-histidyl-proline residues
What is the mechanism of TRH signaling in the anterior pituitary?
GPRC via
- PLC
- IP3
- Ca++
What is the mechanism of TSH signaling in the thyroid gland?
GPRC via
- cAMP protein kinases
Specifically, what does TSH stimulate?
1) Iodide transport
2) Transcription of thyroglobulin
3) Transcruption of tyroid peroxidase (TPO)
What thyroid hormone is preferentially bound to serum proteins?
T4
What enzymes catalyze the metabolism of T3 and T4?
Deiodinases
What are the functions of deiodinases?
1) Formation of active T3 from T4
2) Deactivation of T3 and T4 when their concentrations are too high
What form of deiodinase is active against T3?
Type III
*Thus, this is the major enzyme that deactivates thyroid hormones
What is the function of Type I deiodinase?
Outer/ inner ring vs. T4
Where is Type I deiodinase located?
Liver, kidney, thyroid
What are the products of Type I deiodinase?
T3 or rT3
What is the function of Type II deiodinase?
Outer ring vs. T4
What is the location of Type II deiodinase?
Diffuse
What is the product of Type II deiodinase?
Intracellular T3
What is the function of Type III deiodinase?
Inner ring vs. T4 and T3
Where is Type III deiodinase located?
Brain and placenta
What are the products of Type III deiodinase?
rT3 and T2
Describe the mechanism of action of the thyroid hormones in the nucleus.
1) TR binds DNA with RXR
2) TR/RXR recruits HDAC, repressing transcription
3) Binding of T3 or T4 displaces HDAC for HAT*
HAT complex turns target genes ON
What is stimulated by T3/T4 in regards to cellular metabolism?
1) Increased oxygen consumption/ heat production
2) Increased adipose tissue lipolysis
3) Increased glycogenolysis and gluconeogenesis
