Topic 09-Thyroid-S_2011

Topic 09-Thyroid-S_2011 - 9. Thyroid hormone Click to edit...

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Click to edit Master subtitle style 9. Thyroid hormone A. Anatomy of the thyroid gland & hormone synthesis B. Buffering & signaling mechanism C. Hypothalamic/pituitary feedback D. Function & pathophysiology
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22 The Thyroid n First recognized gland & hormone n Essential in childhood for normal growth & development n Adults: normal metabolism n Only biological role for iodine n Minimal dynamic regulation n Known for pathophysiology
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Thyroid gland 33 Follicles: Colloid + follicular cells C cell (calcitonin) Follicular cells Capsule Capillary Colloid Colloid
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Thyroid hormones are made from iodine and tyrosine Collectively known as “Thyroid hormone” 44 Unique biosynthetic pathway → gland anatomy
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55 Blo od Collo id Follicul ar cell T4 synthesis STEP 1: thyroglobulin provides tyrosine OH OH OH OH OH OH OH OH OH OH Transcribed Translated Transported OH OH OH OH OH OH OH OH OH OH CH 2 OH Tyrosi ne Peptide  Chain n Thyroglobulin ¨ From follicular cells ¨ To colloid n Large: ¨ MW=660K ¨ 5496 aa ¨ 140 tyrosines OH OH OH OH OH OH OH OH OH OH
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66 Blo od Follicul ar cell Collo id STEP 2: Iodine is actively n Iodine ¨ Uptake 80 μ g/day ¨ 8 mg stored n Iodine trap ¨ Sodium- i odine s ymporter ¨ Energy from Na/ K ATPase n Transported to I A T P I I Active Passiv e A D P 2N a+ NI S Pendri n 3N a+ 2 K +
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77 STEP 3: Iodine conjugation to Bloo d Follicular cell O2+I− CH 2 OH thyroglobu H2O 2 CH 2 OH I I CH 2 OH I MIT monoiodoty rosine DI T Thyroid peroxidase complex n Bound to follicular cell apical membrane n Yields iodinated thyroglobulin n Mostly DIT n Some MIT
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88 STEP 4: T4 & T3 form spontaneously I CH 2 OH I CH 2 OH I I CH C O N H I I OH I O CH 2 I n No enzyme required n Between or within thyroglobulin molecules n Attached to thyroglobulin n T4 if DIT the substrate
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99 Blo od Follicul ar cell Proteas es O H O H O O H I I I I O O H I I I I O O H I I I I O O H I I I I O H I I OH O OH I I
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Topic 09-Thyroid-S_2011 - 9. Thyroid hormone Click to edit...

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