Synthesis Of Thyroid Hormone
SYNTHESIS OF THYROID HORMONE
- Thyroid hormone denotes both thyroxines (T4) & triiodothyronine (T3).
- Both T4 & 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 T4 to T3:
- Peripheral tissues convert T4 to T3.
- Target tissues utilize T3 from 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 T4 / T3 synthesis.
Exam Question
SYNTHESIS OF THYROID HORMONE
- Both T4 & 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 T4 / T3 synthesis.
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