ENDOCRINOLOGY Biochemistry of the Thyroid Glands Lec 6

ENDOCRINOLOGY Biochemistry of the Thyroid Glands Lec. 6 Dr. Ali al-bayati

The thyroid gland (Greek thyros “shield”) is shaped like a shield

Step 1: Uptake of Iodine Step 2: Oxidation of Iodine Step 3: Iodination Step 4: Coupling Step 5: Storage Step 6: Utilization Step 7: Hydrolysis Step 8: Release

Iodine Metabolism q The minimum daily iodine to maintain normal thyroid function is 150 μg in adults [1 mg/week] Upper regions of mountains generally contain less iodine. Such areas are called goitrous belts, e. g. Himalayan region. Ingredients in foodstuffs, which prevent utilization of iodine, are called goitrogens. Goitrogens are seen in cassava, maize, millet, bamboo shoots, sweet potatoes and beans. Cabbage and tapioca contain thiocyanate, which inhibits iodine uptake by thyroid. Mustard seed contains thiourea, which inhibits iodination of thyroglobulin

Iodide Trapping q Dietary iodide absorbed by the intestine enters the circulation • Na+/I– symporter [NIS] transports 2 Na+ ions and 1 I– ion into the cell against the electrochemical gradient • Produces intracellular I– concentrations 20 to 100 times as great as plasma concentration q This step is stimulated by TSH.

Oxidation of Iodide ion v Enzyme thyroid peroxidase [TPO] located in the apical membrane. v This second step is stimulated by TSH v Peroxidase is inhibited by Propyl thio-uracil and Carbimazole

Pinocytosis, Proteolysis & Secretion: • Thyroglobulin with hormones are stored in the gland. • Hormones attached to Thyroglobulin are endocytosed and fused with lysosomes • Lysosomal proteases will release T 3 & T 4 from Thyroglobulin • They diffuse to the basal surface of the cell from where they are secreted in the blood. • Iodides inhibit endocytosis of colloid.

Transport of Thyroid Hormones 80% Transthyretin (TTR) 60% q Because of the high affinity to the binding proteins, T 3 and T 4 are released slowly in the tissues. q Numerous factors like illness, medications and genetic factors can influence protein binding. q assay of free hormones [f T 3 and f. T 4] are better indicators of thyroid function

Catabolism of Thyroid Hormones q T 4 has a half-life of 4– 7 days, while T 3 has about 1 day. q Part of the T 3 and T 4 are conjugated with glucuronic acid and excreted through bile, and to a lesser extent, through urine. q Deamination of T 4 produces tetraiodothyroacetic acid (Tetrac); and T 3 gives rise to tri-iodothyroacetic acid (Triac). These are only one-fourth as active as the parent compound.

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