Prof.Dr.Arzu SEVEN Slide 2 Thyroid hormone biosynthesis involves
thyroglobulin and iodide metabolism Slide 3 Slide 4 THYROD HORMONES
1- Concentration of iodide In the follicular epithelial cells,
against a strong electrochemical gradient Energy-dependent process,
linked to ATPase dependent Na + - K + pump Thyroidal I -
transporter (controlled by TSH) odide in thyroid/iodide in serum
ratio reflects the activity of this transporter (25/1) odide
transporter is inhibited by perchlorate and thiocyanate Slide 5 2-
Oxidation of I - by thyroid peroxidase (TPO) in the peroxisome to
iodine As an oxidizing agent, TPO requires H2O2, produced by
NADPH-dependent enzyme (like cytocrome c reductase). Antithyroid
drugs-thiourea-inhibit I - oxidation 3- Iodination of tyrosine
(organification) oxidized ioide reacts with tyrosyl residues in
thyroglobulin (involves TPO) to form MIT or DIT Slide 6
Thyroglobulin: Prohormone Precursor and storage form of T4 and T3
Large, iodinated and glycosylated protein Composed of 2 subunist
Contains 115 tyrosine residues Thyroglobulin is synthesized in the
basal portion of the cell. It is stored in the extracellular
colloid Slide 7 4- Coupling of iodotyrosyls (catalysed by TPO,
inhibited by antithyroid drugs ) DIT + DIT T4DIT + MIT T3 In the
thyroglobuli n molecule Slide 8 5-Thyroglobulin (Tgb) hydrolysis
stimulated by TSH (or cAMP) inhibited by I - ncrease in microvilli
on the apical membrane phagocytosis + pinocytosis, bring Tgb back
into the follicular cell Phagosomes + lysosomes phagolysosomes in
which acid proteases and peptidases hydrolyse Tgb into amino acids
and iodothyronines Slide 9 T3 and T4 are discharged from the basal
portion of cell by facilated process into blood MIT DIT ~ 70% of
iodide in Tgb exists in inactive precursors (MIT, DIT),~ 30% in T4
and T3 Tyrosine deiododinase I-I- Slide 10 When iodine supplies are
sufficient T4/T3: 7/1 In iodine deficiency, T4/T3, DIT/MIT Daily
iodide requirement: 150-200 g Slide 11 Slide 12 Transport of
thyroid hormones Thyroxine binding globulin (TGB) 70% Albumin 25%
Thyroxine binding prealbumin (TBPA) 5% TBG, a glycoprotein, binds
nearly all T4 and T3 noncovalently TBG is produced in liver Its
synthesis is, increased by estrogens,decreased by androgens or
glucocorticoid therapy and in liver disease Phenytoin and
salicylates compete with T3 and T4 to bind to TBG Slide 13 The
small, unbound (free) fraction is responsible for biological
activity Free T4 and T3 is a measure of thyroid hormone status,
represents
