Thyroid hormone synthesis in our body@ mbbs

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

3. 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

4. Outer ring

5. 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 .

6. 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

7. 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 .

8. Biological action Many important biological function . ↑ es O 2 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

9. ↑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

10. 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 Po 4 – metabolism. Also contribute to peristalsis movement.

11. Biosynthesis[pathway] of Thyroid hormones

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

13. 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

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

15. 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]

16. 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]

17. 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 ↓ ↓ ↓ ↓

18. colloid dehalogenase

19. 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.

20. 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.

21. THANK YOU