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9.2.3.1 Membrane bound receptors
For hormones that bind to cell membrane a number of receptors act as second messenger cAMP, cGMP and Ca2++ ions cAMP as the second messenger cAMP is formed from ATP. A receptor, G protein and Adenylate cyclase are needed. cAMP (Cyclic adenosine 3 '-5 ' monophosphate) is formed from ATP by the action of the enzyme adenylatecyclase and then converted to physiologically inactivated 5’–AMP by the action of enzyme phosphodiesterase. The Hormone receptor complex combines with G protein type of GTP dependent trimeric nucleotide regulatory complex of the cell membrane. G protein is made up of 3 subunits , α, b and gama . The α subunit of G is bound to GDP. Then binding of hormone to R results in a receptor mediated activation of G, then GDP is exchanged for GTP and the α subunit separates from the combined beta and gama subunits. This GTP -α subunit activates effectors (adenylatecyclase). Hormones that stimulate adenylatecyclase are ACTH , ADH , FSH, Glucagon. Hormones that inhibit adenylate cyclase are Acetylcholine , Angiotensin II . cAMP binds to a protein kinase. cAMP binding results in the following reaction. 4cAMP + R2C 2 Û R 2 (4cAMP) + 2 C . T h e R2C 2 complex has no enzymatic activity but the binding of cAMP by R dissociates R from' C, thereby activating protein kinase. This activated protein kinase catalyzes the transfer of the phosphate of ATP (Mg ++ ) to a serine or threonine residue in a variety of proteins. Thus, they regulate the conformational changes of phosphoprotein and physiologic effect occurs . |