Cell Signaling and Metabolism Regulation: Understanding the Intricacies
Dive into the world of cell signaling and metabolic regulation with Dr. Reem M. Sallam, exploring the fundamental aspects of signaling pathways, second messenger systems, and the integration of metabolism. Discover how cells communicate, respond to signals, and modulate metabolism for optimal functioning.
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Presentation Transcript
Cell Signaling and Regulation of Metabolism By Dr. Reem M. Sallam, MD, PhD Clinical Chemistry Unit Department ofPathology
Objectives By the end of this lecture, students are expected to: Differentiate different steps in signalingpathways Describe the second messengersystems Recognize the function of signaling pathwaysfor Signal transmission Amplification Discuss the role of signaling pathwaysin regulation and integration of metabolism
No cell lives in isolation Cells communicate with each other Cells send and receive information (signals) Information is relayed within cell to produce a response
SignalingProcess Recognition of signal Receptors Transduction Change of external signal into intracellular message with amplification and formationof second messenger Effect Modification of cell metabolism andfunction
SignalingProcess Recognition of signal Receptors Transduction Change of external signal into intracellular message with amplification and formationof second messenger Effect Modification of cell metabolism andfunction
Recognition Performed by receptors Ligand will produce response only in cells that have receptors for this particular ligand Each cell has a specific set of receptors
Different Responses to the Same Signaling Molecule (A) Different Cells
Different Responses to the Same Signaling Molecule (B) One Cell but, Different Pathways Hypoglycemia Glucagonsecretion Hepatocyte: Glucagon/receptor binding Second messenger: cAMP Response: Enzymephosphorylation P P Glycogen synthase (Inactive form) Glycogen phosphorylase (Active form) Inhibition ofglycogenesis Stimulation ofglycogenolysis
GTP-Dependant Regulatory Proteins (G-Proteins) Trimeric membrane proteins( ) G-stimulatory (Gs) and G-inhibitory (Gi) Binds toGTP/GDP G-Proteins: Forms ofG-Proteins Active form -boundGTP ( /GTP) Inactive form Trimeric boundGDP ( /GDP) The -subunit has intrinsic GTPase activity, resulting in hydrolysis of GTP into GDP and inactivation ofG-proteins
Signaling Pathways for Regulation of Metabolism Two important second messenger systems: Adenylyl cyclase system Calcium/phosphatidylinositol system
Adenylylcyclase Adenylylcyclase: Membrane-boundenzyme Converts ATP tocAMP Activation/Inhibition: Signal: Hormones orneurotransmitters (e.g., Glucagon and epinephrine) orToxins (e.g., Cholera and pertussis toxins) Receptor: G-protein coupledreceptor Response: Activation/inhibition of protein kinase A (cAMP-dependent proteinkinase)
Signal Transduction: Adenylyl Cyclase System Ligand/Receptor Binding Resting state: No Signal Activation of Gs-protein
Signal Transduction: Adenylyl Cyclase System Activation of adenylyl cyclase
Adenylyl Cyclase System: cAMP-Dependent Protein Kinase (Protein KinaseA) * AMP *Phosphodiesterase
Termination of Signal(A) * AMP *Phosphodiesterase Protein phosphatase Phosphodiesterase Inactive protein kinase cAMP
G-Protein Coupled Membrane Receptor
Regulation of Glycogen Metabolism by Glucagon: Effects on Glycogen Synthase and Phosphorylase Hypoglycemia Glucagonsecretion Hepatocyte: Glucagon/receptor binding Second messenger: cAMP Response: Enzymephosphorylation P P Glycogen synthase (Inactive form) Glycogen phosphorylase (Active form) Inhibition ofglycogenesis Stimulation ofglycogenolysis
Pyruvate Kinase Regulation: CovalentModification
Calcium/Phosphatidylinositol System
Calcium/Phosphatidylinositol System Diacylglycerol (DAG) Phospholipase C Inositol Trisphosphate (IP3)
e.g., Antidiuretic hormone(ADH) Acetylcholine Intracellular Signaling by Inositol trisphosphate
Take Home Message Cell signaling allows Signal transmission and amplification Regulation of metabolism Intercellular communications & coordination of complex biologic functions
