Thyroid Biochem and Phys

Question 1

What is the precursor molecule to Thyronine?

Answer 1

Tyrosine (need to add another aeromatic ring)

Question 2

What are the Biologically Inactive THyroid hormones?

Answer 2

T2

rT3 (Iodine on outer ring instead of inner ring)

Question 3

What is the Biochemical makeup of Thyroglobulin?

Answer 3

Homodimer, Glycoprotein
Synthesized in follicular cells
Secreted and stored in colloid
75% of the protein of the thyroid gland

Question 4

What is the transport mechanism used for Iodide?

Answer 4

Na/I symporter(1x I and 2x Na)

Na/K ATPase pumps 3 Na back out

Question 5

What is the effect of Thyroglobulin Organification?

Answer 5

Iodide is added to the Tyrosyl Residues via Oxidation by Thyroid Peroxidase

Question 6

What Enzyme is responsible for organification AND Coupling to create T3/T4?

Answer 6

Thyroid Peroxidase

Question 7

How much Thyroid Hormone is Stored in the THyroid?

Answer 7

2-3 months worth of hormone

Question 8

What is the ratio of T4 to T3?

Answer 8

5-7 x T4 for each T3

Question 9

What happens to the Iodide after use of Thyroid hormone?

Answer 9

Iodide is cycled back and re-used

Question 10

What is the chemical compsition of TRH?

Answer 10

Pyroglutamyl-histidyl-proline residues

Question 11

What second messenger does TRH use in signaling?

Answer 11

TRH => G protein coupled receptor => Phospholipase C => inositol 1,4,5 triphosphate => Ca => secretion of TSH into blood circulation

Question 12

What is the biochemical makeup of TSH?

Answer 12

28-kDa glycoprotein and Heterodimer (a/B subunits)

Question 13

How does TSH stimulate secretion of T3 andT4?

Answer 13

TSH binds to G protein coupled receptor on basolateral membrane
Activation of cAMP-protein kinases
TSH stimulates: Iodide Transport, transcription of thyroglobulin, and TPO

Question 14

What is the negative feedback pathway of the H-P-Thyroid axis?

Answer 14

Increased T3/T4 inhibit:

• TSH transcription
• TSH post-translational mod
• TRH gene expression
• TRH receptor synthesis

When T3/T4 level falls, TSH overcomes inhibition

Question 15

What is the process of deiodination of T3 and T4?

Answer 15

Type 1-3 diodinases
Triggers formation of biologically active T3
Deactivates T4 and T3 when the conc. rises above desireable

Question 16

What are the differences between Type 1-3 deiodinases?

Answer 16

Type 1-O/In ring act. onT4
Type 2- Out ring act. on T4
Type 3- Inner ring act. on T3-T4

Question 17

What type of receptor is used in T3/T4 signaling?

Answer 17

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)

Question 18

What are the biological actions of T3/T4 on cellular metabolism?

Answer 18

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

Question 19

What are the effects of Thyroid Hormone on Bone?

Answer 19

Inc. Bone growth in kids
Osteoporosis if too much
normal skel devt.

Question 20

What are the effects of Thyroid Hormone on The Heart?

Answer 20

Inc. Cardiac output

Inc. Transcription of Ca ATP ase and myosin

Question 21

What are the effects of Thyroid Hormone on The liver?

Answer 21

inc uptake and mets of Cholesterol

lowers plasma Chol

Inc Triglyceride mets lower Serum Trig

Question 22

What are the effects of Thyroid Hormone on Pituitary?

Answer 22

Inhib TSH

Inc GH

Question 23

What are the effects of Thyroid Hormone on Brain?

Answer 23

Brain Maturation

Reg normal brain dev