Thyroid Biochem and Phys Flashcards
What is the precursor molecule to Thyronine?
Tyrosine (need to add another aeromatic ring)
What are the Biologically Inactive THyroid hormones?
T2
rT3 (Iodine on outer ring instead of inner ring)
What is the Biochemical makeup of Thyroglobulin?
Homodimer, Glycoprotein
Synthesized in follicular cells
Secreted and stored in colloid
75% of the protein of the thyroid gland
What is the transport mechanism used for Iodide?
Na/I symporter(1x I and 2x Na)
Na/K ATPase pumps 3 Na back out
What is the effect of Thyroglobulin Organification?
Iodide is added to the Tyrosyl Residues via Oxidation by Thyroid Peroxidase
What Enzyme is responsible for organification AND Coupling to create T3/T4?
Thyroid Peroxidase
How much Thyroid Hormone is Stored in the THyroid?
2-3 months worth of hormone
What is the ratio of T4 to T3?
5-7 x T4 for each T3
What happens to the Iodide after use of Thyroid hormone?
Iodide is cycled back and re-used
What is the chemical compsition of TRH?
Pyroglutamyl-histidyl-proline residues
What second messenger does TRH use in signaling?
TRH => G protein coupled receptor => Phospholipase C => inositol 1,4,5 triphosphate => Ca => secretion of TSH into blood circulation
What is the biochemical makeup of TSH?
28-kDa glycoprotein and Heterodimer (a/B subunits)
How does TSH stimulate secretion of T3 andT4?
TSH binds to G protein coupled receptor on basolateral membrane
Activation of cAMP-protein kinases
TSH stimulates: Iodide Transport, transcription of thyroglobulin, and TPO
What is the negative feedback pathway of the H-P-Thyroid axis?
Increased T3/T4 inhibit:
- TSH transcription
- TSH post-translational mod
- TRH gene expression
- TRH receptor synthesis
When T3/T4 level falls, TSH overcomes inhibition
What is the process of deiodination of T3 and T4?
Type 1-3 diodinases
Triggers formation of biologically active T3
Deactivates T4 and T3 when the conc. rises above desireable
What are the differences between Type 1-3 deiodinases?
Type 1-O/In ring act. onT4
Type 2- Out ring act. on T4
Type 3- Inner ring act. on T3-T4
What type of receptor is used in T3/T4 signaling?
Inter-nuclear receptor. Thyroid receptor heterodimer is constitually bound to DNA.
Displaces HDAC with HAT and turns on DNA transcription
(Retinoid Receptor is the other part of the Recpetor)
What are the biological actions of T3/T4 on cellular metabolism?
Increased O2 consumption in the Mitochondria -ATPase -uncoupling Increases adipose tissue lipolysis -LPL activated -FAs used for thermogenesis Increased glycogenolysis and gluconeogenesis -glucose used for thermogenesis
What are the effects of Thyroid Hormone on Bone?
Inc. Bone growth in kids
Osteoporosis if too much
normal skel devt.
What are the effects of Thyroid Hormone on The Heart?
Inc. Cardiac output
Inc. Transcription of Ca ATP ase and myosin
What are the effects of Thyroid Hormone on The liver?
inc uptake and mets of Cholesterol
lowers plasma Chol
Inc Triglyceride mets lower Serum Trig
What are the effects of Thyroid Hormone on Pituitary?
Inhib TSH
Inc GH
What are the effects of Thyroid Hormone on Brain?
Brain Maturation
Reg normal brain dev
