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: Water soluble hormones Receptor: membrane receptor Receptor: membrane receptor Hormone + Recep: Activate G‐protein (transducin) on innerside of membrane Activate adenylcyclase CAMP Third messenger Third messenger Phosphlipase C DAG Second messengers release of ca++from ER activate protein kinase C release of ca++from ER activate protein kinase C IP3 activate protein kinase A activate protein kinase A Ca++ +calmodulin Phosphorylation Phosphorelation Activate protein kinase dependant on ca/calmodulin Phosphorylation Diseases resulting g from receptor p defect: Biosynthesis of peptide Hormones: Parathyroid H as an example Steps: 1. initiation ► formation of a mRNA Specify a polypeptide larger than required one On ribosome translation On ribosome translation .2 2 20 aminoacyl residue (peptide)formed (signal peptide) y (p p ) ( g p p ) 3. Signal peptide facilitate ‐growing polypeptide chain ‐associated mRNA ‐Ribosome to ER Ribosome to ER Contnued to next slide Growth of the polypeptide continue and glycosylation if needed take place & before the formation complete signal peptide removed by peptidase tid db tid .4 Prohormone is formed (inactive) 5 By energy – requiring step (GTP) prohormone is transferred to golgi further glycosylation take place if necessary 6 Active hormone formed by peptidase ‐two peptides are formed some times both have biological function two peptides are formed some times both have biological function 7 On signal to secrete Ca++ dependent fusion of vesicle with plasma membrane ► release of hormone plasma membrane ► release of hormone 8 THYROID HORMONES Structure and biosynthesis of T3 and T4 Structure and biosynthesis of Steps: 1‐ Iodide uptake Iodide uptake from blood energy dependent uptake inhibited from blood energy dependent uptake inhibited by perchlorate 2‐ iodide► free radicle I+ iodination on tyrosine molecules which present on surface of on tyrosine molecules which present on surface of 3‐ 3 thyroglobulin by peroxidese on position 3 mono iodotyrosin thereon position 5 di iodiotyrosin 4‐ by peroxidese Coupling will take place between 2 diiodotyrisine► will take place between 2 diiodotyrisine► T4 Or between monoand& diiodotyrosine► T3 Both T3&T4 will be on the surface of thyroglobulin Both T3&T4 will be on the surface of thyroglobulin Contnued to next slide by effect of TSH 5‐ Th Thyroglobulin transferred by l b li t f d b pinocytosis i t i from colloid 6‐ Thyroglobulin vesicle fuse with lysosome► proteolysis ▼ T3, T4 , mono and diiodotyrosine 7‐ T4: T3 20‐30 :1 0 30 : T3► 3‐5 times more potent than T4 T4 deiodinase T3 In prepreferal tissue In prepreferal tissue T3 T4 Prohormone true hormone Plasma transport of T3 and T4 Plasma transport of T3 and T4 > 99.5% are bound • Binding proteins: d • Thyroxine‐binding globulin • Albumin • Precalbumin • albumin 20 % 20 % 35 % prealb 10 27 TBG T4 70 T4 70 T3 38 Protein bound are biologically inactive►Reserve g y Inactivation of T3 &T4 T4 deiodination T3 + rT3 T3, rT3 deiodinated bis ‐iodothyronines Transport of T3 and T4 In the plasma, T3 and T4 are mostly , about 99.5%, bound to transport proteins. p p Albumin Thyroxine-binding globulin Prealbumin T3 25% 75% none T4 10% 75% 15% Thyroxine‐binding globulin is a special α‐ globulin of molecular weight 60,000. The concentration in plasma is very low, 2 mg/100ml, but it has one binding site per molecule with a very high affinity for T4 and T3. 3. Peripheral hormone conversion 3 P i h lh i by conversion of T4 into active T3 or inactive rTT3 as a response of a variety of physiologic f i t f h i l i and pathologic changes and determining the b l balance between hormone activation and b t h ti ti d inactivation, e.g. malnutrition, liver disease, generalized debility, pregnancy, stress and li d d bilit t d steroid therapy increase rT3