Synthesis Of Thyroid Hormone

Synthesis Of Thyroid Hormone


SYNTHESIS OF THYROID HORMONE

  • Thyroid hormone denotes both thyroxines (T4) & triiodothyronine (T3).
  • Both T& T3 are iodine derivatives of thyronine.
  • Thyronine – condensation product of 2 molecules of amino acid tyrosine.
Chemical structure:
  • Thyroxine: 3, 5, 3′, 5′-tetraiodothyronine.
  • T3: 3, 5, 3′-triiodothyronine.
Synthesis:
  • Synthesized & stored within thyroglobulin molecule of thyroid follicles.

STEPS IN PRODUCTION:

  • 5 Major steps are involved – 
  • Iodide uptake
  • Oxidation & Iodination
  • Coupling
  • Storage & Release.
  • Peripheral conversion of T4 to T3

1. Iodide uptake

  • First step in synthesis.
  • Uptake via “Secondary active transport” – Na2+: I symporter in follicular cells.
  • Trapping is TSH stimulated.

Na2+: I symporter also found in,

  • Skin
  • Salivary glands
  • Gastric mucosa
  • Intestine
  • Mammary glands.
  • Placenta.
  • Uptake in these organs is not stimulated by TSH.

2. Oxidation and iodination:

  • Trapped iodide transported to colloid.
  • Inside colloid oxidized by membrane-bound thyroid peroxidase.
  • Converted to oxidized forms of iodine:
  • Iodinium ion (I+) / Hypoiodous acid (HOI)/enzyme-linked hypoiodite (E-OI).
  • Combine with tyrosine residues of thyroglobulin —> Mono-Iodotyrosine (MIT) & Di-Iodotyrosine (DIT)

3. Coupling:

  • Oxidation reaction.
  • Catalyzed by membrane-bound thyroid peroxidase. 
  • Pairs of iodinated tyrosine residues couple together forming T3 & T4.
  • Oxidation & coupling are TSH stimulated. 

4. Storage & release:

  • Thyroglobulin containing MIT, DIT, T3 & T4 transported into follicular cells by endocytosis.
  • Broken down by lysosomal proteases inside follicles.
  • Releases T4 & T3 into circulation.
  • Uptake (endocytosis) & proteolysis of thyroglobulin – TSH stimulated.
  • Releases MIT & DIT are de-iodinated.
  • Iodide released is reutilized. 
  • Thyroid hormones stored in thyroid follicles for 2-3 months, bound to thyroglobulin.

5. Peripheral conversion of Tto T3:

  • Peripheral tissues convert Tto T3.
  • Target tissues utilize Tfrom circulation.
  • Except in brain & pituitary.
  • Take up T4 → Convert it to T3 within their own cells.
Wolff- Chaikoff Effect:
  • Excess iodide inhibits its self-transport within thyroid cells.
  • May alter cells redox potential interfering iodination.
  • Results in ↓ed T/ T3 synthesis.
Exam Question
 

SYNTHESIS OF THYROID HORMONE

  • Both T& T3 are iodine derivatives of thyronine.
  • Thyronine – condensation product of two molecules of amino acid tyrosine.

PRODUCTION STEPS:

  • Iodide uptake via “Secondary active transport”- Na2+: I symporter in folllicular cells.
  • Trapping is TSH stimulated.
  • Na2+: I symporter also found in,
  • Salivary glands.
  • Mammary glands.
  • Placenta.
  • Oxidation, iodination, coupling & thyroglobulin proteolysis are TSH stimulated. 
  • Thyroid hormones are stored in thyroid follicles for 2-3 month.
  • Wolff- Chaikoff Effect:Excess iodide inhibits its self-transport in thyroid cells, results in reduced T/ T3 synthesis.
Don’t Forget to Solve all the previous Year Question asked on Synthesis Of Thyroid Hormone

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