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This document summarizes the cyclic AMP pathway, which is a major intracellular signaling pathway utilized by many hormones and extracellular molecules. It involves hormones binding to cell surface receptors and activating G proteins, which then activate the enzyme adenylyl cyclase. This leads to formation of the second messenger cyclic AMP (cAMP) from ATP. cAMP then activates protein kinase A and causes phosphorylation of target proteins, amplifying the hormone signal and eliciting a physiological response. The document lists many hormones that use this cAMP pathway and outlines the key steps of receptor activation, G protein activation, adenylyl cyclase activation, cAMP formation, and protein kinase A activation. It also discusses how cAMP signaling is terminated by
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Laya k pillai
- 1. CYCLIC AMP PATHWAY LAYA KPILLAI Roll no: 85
- 2. INTRODUCTION • The extracellularmolecules(hormones) that bind to a receptor is the 1st messenger of a pathway. • Hormones forms HR complex and eventually leads to formation of second messengers. • Second messengers are intracellular non-protein, water soluble signal molecules that spread throughout a cell by diffusion. • They relay signals for receptors on cell surface to target molecules inside cells. It significantly amplifies the strength of signals. • One of major second messenger is cyclic AMP (CYCLIC ADENOSINE MONOPHOSPHATE) • Earl Wilbur Sutherland Jr., discovered second messenger for which he won 1971 Nobel prize.
- 3. Hormones that usethe adenylyl cyclase- AMP Pathway ACTH Angiotensin-2 (epithelial cells) Calcitonin Catecholamines CRH FSH Glucagon HCG LH PTH Secretin Somatostatin TSH Vasopressin
- 4. STEPS INVOLVED….. Step1: BINDING OF HORMONE to a specific receptor in the cell membrane Step2: ACTIVATION OF G-PROTEIN after the formation of HR complex, GDP is replaced by GTP. Step3: ACTIVATION OF ENZYME ADENYLATE CYCLASE activated G-protein either stimulates or inhibits the enzyme adenylate cyclase which is located in plasma membrane Step4: FORMATION OF cAMP the part of enzyme adenylyl cyclase protrudes through the inner surface of the cell membrane and when activated it catalyse the formation of cAMP from cytoplasmic ATP with Mg2+ as cofactor. Thus a stimulatory G-protein increases the cAMP level whereas inhibitory G protein decreases the cAMP level. Step5: Action of cAMP: it activates protein kinase A. One molecule of cAMP stimulates many enzyme, therefore even a slightest amount of hormone acting on cell surface can initiate a powerful response.
- 5. TERMINATION OF CYCLIC-AMPACTIONS The actions of cAMP in the cell are terminated In two ways: 1. cAMP is degraded to 5’-AMP in the cell by the cytoplasmic enzyme Phosphodiesterase (PDE) 2. Serine or threonine specific phosphatases dephosphorylates the protein already phosphorylated by PKA.
- 7. PLASMA MEMBRANE G PROTEIN ADENYLYLCYCLASE (activated) ECF R H ATP cAMP Mg2+ Activates the protein kinase A Phosphorylation Physiological response 5’AMP(Inactive) PDE ICF
- 8. CLINICAL IMPORTANCE Not only,many hormones act through Camp but also, toxins released by various pathogens by altering cAMP concentration in the cell • STIMULATION OF cAMP: as in the case of cholera • INHIBITION OF cAMP: as in case of pertussis, A component of pertussis toxin decreases adenylyl Cyclase activity by inhibitory G protein. This impairs the host’s defense ability
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