Biosynthesis of thyroid hormones. It helps to understand how the thyroid hormones are synthesized from our body form tyrosine and iodine. What are the steps involved in the biosynthesis?

1. BIOSYNTHESIS
OF
THYROID HORMONE
Binaya Tamang
UCMS-TH

2. Introduction
• Thyroid hormone  by thyroid gland [ butterfly
shaped]
• Secretory unit is thyroid follicle
• Outer layer of epithelial cells
• Colloid [ amorphous material  Thyroglobulin
and thyroalbumin]
• Also has parafollicular or ‘C’ cells calcitonin

4. Biochemistry of TH
• TWO hormones
• Thyroxine [T4][ primary secretory product]
• Triiodothyronine[T3]
• In addition , small amount of
• Reverse triiodothyronine [ rT3]
• Monoiodotyrosine[MIT]
• Diiodotyrosine[DIT]
• rT3 is biologically inactive

5. Outer ring

7. Further info..
• Half life of T4 [ 4-7 days] and T3 is about 1 day.
Out of total T4 secreted
↓
Deiodinase enz.[se] in peripheral tissue
↓
40%T3 and 45%rT3
• T3: peripheral deiodination of outer ring of T4.
• rT3: peripheral deiodination of inner ring of T4.

8. • 85% of daily T3 production is due to peripheral
deiodination of T4 rather than direct secretion
from TH. gland.
• T3 is 4-5 times more potent than T4 in biological
system
• Unbound i.e., free T3 and free T4  biologically
active. concept of Free vs bound

9. concept of Free vs bound
• Both T3 & T4 are bound reversibly and almost
completely to carrier protein
• Thyroxine binding globulin [TBG] [ Predominant]
• Thyroxine binding prealbumin[TBPA]
• Albumin
• In collectively, 99.97% of T4 & 99.7% of T3 is bound
• So, fT4 [0.03%] & FT3 [0.3%] free thyroid
hormone actual biological function.

10. Biological action
Many important biological function.
• ↑ es O2 consumption in almost all metabolically
active tissue.
• ↑ the activity of Na+-K+ pump. Na+-K+ ATPase
activity is directly correlated to TH hormone.
• Basal metabolic rate (BMR) is ↑ ed.
• ↑ thermogenesis

11. • ↑es mitochondrial metabolism[ mito. Respiration
and ox. Phosphorylation]
• ↑ es the sensitivity of adrenergic receptors to
catecholamines.
• Stimulate adrenergic activity with ↑ ed heart rate
and myocardial contractility
• Stimulation of RNA synthesis and consequent
protein synthesis acts like steroid hormone

12. • Stimulate neural development and normal growth
• Promote sexual maturation
• Promote intestinal absorption and utilization of glucose.
↑ es gluconeogenesis and glycogenolysis
• Fatty acid metabolism is ↑ed . Lipid turnover and
utilization is stimulated. ↓ TH ↑ cholesterol.
• ↑ es the Ca++ and Po4
– metabolism.
• Also contribute to peristalsis movement.

13. Biosynthesis[pathway]
of
Thyroid hormones

15. Steps of synthesis
• Normally iodide [I-] is trapped from
circulating plasma.
• Follicular cell concentrate iodide to 30-40
times plasma conc by iodine pump[Na/I
sym].
• Rate limiting step: Iodide transport to follicle
is 1st and R.L step.

16. 1.Uptake of iodine
• Thyroid gland takes up and concentrates
iodine by Na/I symporter
• Energy requiring process [ Na+-k+ ATPase
pump]
• Anti thyroid agent such as thiocyanate
perchlorate and pertechnetate inhibit iodine
transport  inhibit iodide transport

18. 2.Oxidation of Iodine [ Active iodine]
• The thyroid is the only organ which can
perform this oxidation step.
• by the enzyme thyroperoxidase [ TPO]

19. 3.Iodination of Tg [ Tyrosine residue]
• Tg[ 660Kda] contains tyrosine residue.
• Active Iodine will bind to tyrosine residue of Tg
organification MIT and DIT
• by thyroperoxidase [ TPO]

20. 4. Coupling
• Coupling or condensation is also done by TPO.
• DIT+DIT T4
• DIT+MITT3
• Occurs at follicular cell-colloid interface and also
with in colloid.
• Formed TH hormones are stored in colloid [
approx. 3 months]

22. 5.Release
TSH
Globules [colloid] endocytosed by follicular cells
Lysosomal protease breaks down peptide bond
of Tg
T3 and T4  circulation
MIT&DIT deiodinated by dehalogenase
Free iodides are then reutilized
↓
↓
↓
↓

23. colloid
dehalogenase

24. TSH almost effects each steps
• ↑es Iodine pump activity.
• ↑es thyroglobulin synthesis
• ↑es organification
• ↑es colloidal uptake by follicular cells
• ↑es rate of proteolysis
• Also, ↑es in the size and no. of TH follicular cells.

25. Metabolic fate of T3&T4
• Conjugates with glucuronic acid or sulphate in liver
• Excrete through bile
• Also, deamination to produce
• tetraiodothyroacetic acid[T4]
• triiodothyroacetic acid[T3]
• Undergo conjugation and excretion.

26. THANK YOU