Thyroid
- 1. Vitamins K and Cبسم الله الرحمن الرحيمBlock: Head & Neck Structure and FunctionBiochemistryLecture: Thyroid hormonesIntroduced by: Dr/Abousree El-Lethy
- 2. Objectives of Thyroid HormonesName the different tyrosine-derived thyroid hormones and list the steps of their synthesis explaining the role of iodine.
- 3. Mechanisms of storage, secretion, transport, degradation and excretion of tyrosine-derived thyroid hormones.
- 4. Metabolic effects of tyrosine-derived thyroid hormones.Tyrosine -derived thyroid hormones1- Tetraiodothyronine (thyroxine; T4).2- Triiodothyronine (T3).Synthesis of thyroid hormoneThyroid hormone synthesis occurs in the follicular space of thyroid gland.
- 5. These hormones require:Thyroglobulin(large protein molecule TG )Iodine About 70% of the iodide in TG exists in the inactive precursors, monoiodotyrosine (MIT) and diiodotyrosine (DIT), while 30% is in the iodothyronyl residues, T4 and T3The amino acid tyrosine is the starting point in the synthesis
- 6. Synthesis of thyroid hormone based the following steps:Step 1: Uptake and concentrate of I-The thyroid is able to concentrate I− in luminal surface of the follicular cell.
- 7. This energitic process is linked to the (Na+-K+ ATPase pump).
- 8. Uptake of thyroidal I− is stimulated by TSH and inhibited by excess of iodine.Step 2: Oxidation of iodine (organification)Iodide is converted to iodine based hyroperoxidase (tetrameric protein) that requires hydrogen peroxide as an oxidizing agent.
- 9. The H2O2 is produced by an NADPH-dependent enzyme resembling cytochromec reductase.Step (3): IodinationIodide is condensed onto tyrosine residues which reside along thyroglobulin resulting in either a mono-iodinated tyrosine (MIT) or di-iodinated tyrosine (DIT) being incorporated into thyroglobulin.Step (4): coupling reactionIodotyrosine molecules are coupled together within the thyroglobulin.
- 10. Coupling two di-iodotyrosine molecules results thyroxin (T4).
- 11. Coupling a di-iodotyrosine and a mono-iodotyrosine results tri-iodothyronine (T3).Step (4)Step (3)Follicular spacecouplingStep (2) Thyroid cellExtracellular space (Blood)Step (1)Outline synthesis steps of thyroid hormnes
- 12. Mechanism of Storage& secretionThyroid hormones are stored in an intracellular reservoir (colloid) in the follicular space
- 13. Thyroid cell is stimulated by TSH, then colloid re-enters the cell by of phagolysosome activity (pinocytosis ).
- 14. Lysosomes produced various acid proteases to hydrolyze the thyroglobulins to release T4 and T3 into blood stream.
- 15. Excess of mono and diiodothyroninemolecules in the thyroid are deionated by to removes I− from the inactive
- 16. The I− is reused again in T3 and T4 biosynthesis by thyroid cell.Colloid (Thyroglobuline) Thyroid cellBlodOutline storage and secretion of thyroid hormnes
- 17. Mechanism of TransportThyroid hormones are lipophilic with intracellular receptors and transported in blood by noncovalently binding proteins carriers like: Thyroxine binding globulin(TBG)Thyroid binding pre-albumin(TBPA) Albumin.Most of this circulates in bound form ( inactive) with (TBG) and (TBPA).
- 18. Unbound (free) fraction is responsible for the biologic activity. therefore, measuring total thyroxine in the blood can be misleading.Mechanism of degradation and Execration Thyroid hormones (T3&T4) are degraded in peripheral tissues by total deiodinationand inactivation based following steps:Step (1): Deiodinated and decarboxylatedStep (2): Glucuronidation and sulfation in the liver to produce hydrophilicsStep (3): Excretion in bile duct secretions into gut.Step (4): Excretion of glucuronide conjugate in urine through kidney.
- 19. Metabolic effects of thyroid hormones: (Functions of T3 & T4)Increasing oxygen consumption in most of the body tissues.It promote protein synthesis by enhancing transcriptional level.It promotes intestinal absorption and utilizationofglucose.Increasing blood glucose level by activation of glycogenolysis& gluconeogenesis.Stimulation of lipid turn over and utilization are stimulated by. Hence hypothyroidism is associated with elevated cholesterol level.Regulation of water and electrolyte metabolism.