Topic 2 - Intracellular Signalling Pathways PDF

🚦 Topic 2 - Intracellular Signalling Pathways LECTURE 1 What are the 4 sections of signal transduction signals - ligand receptors - recognise signalling molecules, cause a...

🚦 Topic 2 - Intracellular Signalling Pathways LECTURE 1 What are the 4 sections of signal transduction signals - ligand receptors - recognise signalling molecules, cause a confirmation change transduction - signalling cascade with secondary messengers response - regulation of cellular activities How are signalling molecules recognised? membrane receptors (such as GPCRs)* intracellular receptors Topic 2 - Intracellular Signalling Pathways 1  What does “GPCR” stand for G protein-coupled receptor (Cell receptors linked to a G protein on the plasma membrane) G-protein coupled receptors – Give a general overview of how they work in the plasma membrane ligand binds to receptor on plasma membrane activates G-protein G-protein activates effector generates “secondary messengers” What are Agonists Bind to the receptor and activate it (leading to intracellular signal transduction events). Topic 2 - Intracellular Signalling Pathways 2  What are Antagonists Bind to the receptor, but do not activate it (block the effects of agonists at the receptor) What is the structure of the Receptor part of GPCRs They are Membrane receptors (except rhodopsin) Single a-helix polypeptide chain 7-Transmembrane regions (H) Extracellular (E) and cytosolic regions (C). Extracellular N-terminal + Cytosolic C-terminal Topic 2 - Intracellular Signalling Pathways 3  What is the structure of G-Protein in GPCRs G-proteins = Guanine nucleotide (GTP) binding proteins Heterotrimeric made up of 3 subunits: alpha (a), beta (β) and gamma (γ) Gα, which carries the binding site for the nucleotide (GDP, GTP) Gβ (beta) Gγ (gamma) GPCR interaction is activated since G protein exchanges GDP for GTP Explain how a GPCR functions specifically Topic 2 - Intracellular Signalling Pathways 4  ligand binds to receptor at the 7-transmembrane region nucleotide exchange at the α subunit, GDP → GTP activation occurs, alpha subunit dissociates subunits carry on signal transduction + amplification after binding to receptor is finished at 6, signalling quantity decreases alpha unit is favoured back to its resting confirmational state (GTP → GDP) What are the 4 names of the active alpha subunit 4 names recognise the secondary messengers they cascade Topic 2 - Intracellular Signalling Pathways 5  What is the outcome of activation of a Gs or Gi active alpha subunit adenylyl cyclase/cAMP signalling activity What is the outcome of activation of a G12/13 active alpha subunit small GTPase families What is the outcome of activation of a Gq active alpha subunit activates phospholipase C /IP3/DAG Signalling pathway (target enzyme) What are the 3 names of the active beta-gamma subunit What is Adenyl Cyclase (Effectors) enzyme that changes bonds in ATP molecule (linear → Cyclic structure) produces cAMP (secondary messenger) (can be activated/inhibited by different ligands) Signal Amplification Topic 2 - Intracellular Signalling Pathways 6  magnifies and enhances signals received by cells, particularly during various signalling pathways. This amplification is essential for cells to respond effectively to extracellular stimuli and orchestrate complex cellular responses LECTURE 2 What hormone regulates Ca levels Parathyroid hormone is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration Why is calcium an essential element in the body Topic 2 - Intracellular Signalling Pathways 7  important role in skeletal mineralisation >99% of calcium in the body is found in the bones of the skeleton. 11 mg/dL What level is Hypocalcaemia Hypocalceamia - calcium levels are < 8.5 mg/dL Where is the largest conc. of Calcium found in cells Endoplasmic Reticulum Explain in simple terms how Calcium Sinks work cytoplasm/cytosol acts a sink calcium flows from extracellular matrix calcium flows through cytoplasm calcium stored in SR/ER (smooth endoplasmic reticulum) What is PMCA Ca2+ transport, ATPase Topic 2 - Intracellular Signalling Pathways 9  transporter that requires ATP, releases calcium from cytosol to extracellular matrix maintains low cytosolic Ca2+. What is NCX Na+/Ca2+ exchanger (NCX) transporter mechanism from cytosol to extracellular matrix no need for ATP maintains low cytosolic Ca2+ What is SERCA transporter ATP Dependant fills the smooth endoplasmic reticulum’s Ca2+ storage from Cystolic Ca2+ Topic 2 - Intracellular Signalling Pathways 10  What are the 4 mechanisms/channels that increase intracellular Ca2+ Ca2+ ion channels: selectively permeable for calcium ions Voltage-gated calcium channels: open in response to cell depolarization Ligand-gated ion channels: opened by ligand binding Store-operated channels What is Calmodulin protein that binds to calcium Calmodulin has 4 binding sites for calcium calmodulin will move and activate other proteins What is the Clinical use of calcium channel blockers Calcium channel blockers are medications used to lower blood pressure. Topic 2 - Intracellular Signalling Pathways 11  blocks calcium influx By blocking calcium, calcium channel blockers allow blood vessels to relax and open. Topic 2 - Intracellular Signalling Pathways 12