Biochemistry Unit 12 Thyroxine & Metabolic Effect PDF

THYROXINE AND ITS METABOLIC EFFECTS BBM1233 MEDICAL BIOCHEMISTRY 2  Learning Objectives At the end of this lecture, the student will be able to: Describe the synthesis of thyroid hormone Explain the functions of thyroid hormone ANATOMY OF THYROID GLAND  one of the...

THYROXINE AND ITS METABOLIC EFFECTS BBM1233 MEDICAL BIOCHEMISTRY 2  Learning Objectives At the end of this lecture, the student will be able to: Describe the synthesis of thyroid hormone Explain the functions of thyroid hormone ANATOMY OF THYROID GLAND  one of the largest endocrine gland in the body  butterfly-shaped, has two lobes connected by isthmus  situated on the front sides of the trachea and located below the larynx ❑ Thyroid follicle is the functional unit A spherical structure lined with follicular cells Follicular cavity is usually filled with gel-like viscous iodine-rich material called thyroid colloid (containing protein called thyroglobulin) ❑ Parafollicular cells (C cells) presents between the follicles Secrete calcitonin FUNCTIONS OF THYROID GLAND  Thyroid gland secrete: 1. Thyroid hormone (body’s major metabolic hormone) Thyroxine or tetraiodothyronine (T4) – contain 2 tyrosine molecules + 4 bound iodine atoms Triiodothyronine (T3) – contain 2 tyrosine molecules + 3 bound iodine atoms Both secreted by thyroid follicular cells Regulate body’s metabolic rate and necessary for normal growth and development 2. Calcitonin Synthesizeby the parafollicular cells Decreased blood calcium level CONTROL OF THYROID HORMONE SYNTHESIS & SECRETION  The thyroid gland is controlled by hormone secretions from the hypothalamic-pituitary-thyroid axis  Hypothalamus secretes thyrotropin releasing hormone (TRH)  TRH stimulates secretion of thyroid stimulating hormone (TSH) from anterior pituitary  TSH stimulates T3 and T4 production from the thyroid gland  T3 and T4 exert –ve feedback on the pituitary and hypothalamus. SYNTHESIS OF THYROID HORMONE Thyroglobulin is synthesized in the follicular cells and discharged into the lumen of the follicle 1 Iodide (I-) is actively taken up from the blood by 2 follicular cells through sodium-iodide symporter Once inside the cell, iodide is oxidized to active iodine (I2) by thyroperoxidase (TPO) 3 Iodine is then transported into the lumen of the follicle  Iodine is attaches to tyrosine (amino acid of thyroglobulin), forming Mono-iodotyrosine (MIT) 4 and Di-iodotyrosine (DIT) Iodinated tyrosines link together to form Tri- iodothyronine (T3) and Tetra-iodothyronine or 5 Thyroxine (T4) T4 - formed from 2 molecules of DIT T3 - formed from 1 molecule of DIT and MIT When the need arises, thyroglobulin colloid is then endocytosed and fused with lysosomes, where T3 and 6 T4 are cleaved and diffused into the bloodstream. TRANSPORT OF THYROID HORMONE  Thyroid hormones are hydrophobic  Thus, they are found in the circulation associated with plasma/binding proteins: ◼Thyroxine -Binding Globulin (TBG) (~ 70%) ◼Pre-albumin (transthyretin) ◼Albumin  Less than 1% of thyroid hormone is found free in the circulation. METABOLISM OF THYROID HORMONE  Approximately 100 μg of thyroid hormones are secreted from the gland each day, mostly in the form of T4 with about 10% as T3 About 80% of T4 undergoes peripheral conversion to the more active T3 in the liver and kidney or to reverse T3 (r T3). Physiologically active T3 I1 I2 De-iodination I1 I2 I3 I4 I3 Physiologically inactive de-iodinase reverse T3 (rT3) T4 T3 METABOLISM OF THYROID HORMONE MECHANISM OF ACTION T3 enters into nucleus and binds to a specific nuclear thyroid hormone receptor (TR), which in turn binds to DNA at specific sequence called thyroid hormone response element (TRE) Increases the expression of a variety of different genes that code for proteins that regulate cell functions FUNCTIONS OF THYROID HORMONE