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Flashcards

Signal Transduction

Jacob Coe FoM Year 1 University - Medicine English 44 cards

Cards in this deck (44)

  1. 1Define: Autocrine.Cell signalling with itself via expressed receptors on its own surface.
  2. 2Define: Paracrine.Cell signalling with adjacent cells.
  3. 3Define: Endocrine.Cell signalling with distant cells via the circulation.
  4. 4Suggest 2 examples of signalling molecules.Any from:
    Neurotransmitters
    Hormones
    Growth Factors
    Cytokines
    Vitamin A & D derivatives
  5. 5From what molecule are eicosanoids derived?Arachidonic acid
  6. 6What methods of signalling are common with eicosanoids?Autocrine & Paracrine
  7. 7What effect do NSAIDs have on eicosanoid synthesis?NSAIDs reduce eicosanoid synthesis.
    They inhibit cyclo-oxygenase.
  8. 8What ligands are involved in intracellular signalling pathways?Sex steroids (e.g., oestrogen & testosterone).
    Glucocorticoids (e.g., cortisol).
    Mineralocorticoids (e.g., aldosterone).
  9. 9Why can signalling molecules cross the plasma membrane?They are hydrophobic.
  10. 10To what do steroid hormone-receptor complexes bind?Hormone Response Elements (HRE) of a gene.
  11. 11What is the effect when steroid hormone-receptor complexes bind to the HRE?The promoter is activated.
    Gene transcription begins.
  12. 12How is Nitric Oxide formed & what enzyme catalyses this reaction?Formed from arginine & oxygen.
    Nitric Oxide Synthase
  13. 13When does NO act as a primary messenger?Primary messenger in smooth muscle relaxation.
  14. 14When does NO act as a secondary messenger?Secondary messenger in autocrine signalling.
  15. 15What molecule does NO activate?Guanylyl cyclase.
  16. 16What is the effect of activating guanylyl cyclase?Guanylyl cyclase converts GTP into cGMP
    (a secondary messenger).
  17. 17What is the function of cGMP?cGMP activates a kinase --> phosphorylates target proteins --> relax smooth muscle & vasodilation.
  18. 18How is cGMP degraded?Phosphodiesterase 5 (PDE 5) catalyses cGMP.
  19. 19What is the effect of inhibiting phosphodiesterase 5?cGMP remains active for a longer duration --> leads to a physiological outcome
    (e.g., Viagra).
  20. 20What is the function of GTPases?tBind to GTP & hydrolyse it to GDP.
  21. 21What is the function of phosphodiesterases?Catalyse phosphodiester bonds in cyclic nucleotides (e.g., cAMP or cGMP).
  22. 22What is the function of kinases?catalyse the transfer of a phosphate group from a donor to an acceptor.
  23. 23What is the function of a phosphatase?Facilitates the hydrolysis of organic phosphates in a specific environment.
  24. 24What are the 3 domains within a receptor?1. Extracellular domain
    2. Transmembrane domain
    3. Intracellular domain
  25. 25What are the 2 rapid effects of signalling with plasma membrane receptors?1. Rapid effects on intracellular electrolyte concentrations.
    2. Activation or inhibition of enzymes.
  26. 26Describe the structure of a GPCR.7 transmembrane domains.
    Bind to G protein.
  27. 27Is there kinase activity at a GPCR?No. As the signal is transduced through the G protein instead of a kinase.
  28. 28Are G proteins inhibitory or stimulatory?Both stimulatory & inhibitory.
  29. 29Explain the mechanism of GPCR signal transduction.1. Ligand binds to GPCR.
    2. The G protein exchanges GDP for GTP.
    3. Activated G protein stimulates adenylyl cyclase.
    4. Adenylyl cyclase produces cAMP (secondary messenger).
    5. cAMP activates downstream protein kinase A.
  30. 30In what 2 ways can cAMP elicit a response using protein kinase A?1. Phosphorylates a large number of metabolic enzymes in the cytosol.
    2. Alters gene transcription in nucleus.
  31. 31Briefly explain signal amplification..1 receptor-ligand complex activates many G proteins.
    Each G protein activates many adenylyl cyclases.
    Each adenylyl cyclase converts multiple ATP into cAMP.
    Each cAMP activates multiple protein kinase A.
    Each protein kinase A activates multiple molecules of the target enzyme.
  32. 32How can signal amplification be switched off?1. Enzymatic degradation of GTP to GDP.
    2. cAMP can be degraded by phosphodiesterases.
  33. 33What other molecule can GTP-bound G proteins activate?Phospholipase C.
  34. 34What is the function of Phospholipase C?Degrades phosphatidylinositol in plasma membrane.
  35. 35What is the effect of catalysing phosphatidylinositol?Releases inositol triphosphate (IP3).
  36. 36What happens to the inositol triphosphate?IP3 enters the cytosol & leaves diacylglycerol in its place.
    It diffuses through the cytosol to the ER & binds to receptor --> opens calcium channel.
  37. 37What is the effect of the influx of calcium & diacylglycerol?Activate Protein Kinase C.
  38. 38What causes Retinitis pigmentosa?Mutations in the transmembrane domain of Rhodopsin GPCR.
  39. 39In what 2 ways can Receptor Tyrosine Kinases be activated?1. Growth & Differentiation Factors
    (e.g., EGF).
    2. Metabolic regulators (e.g., insulin).
  40. 40Explain the mechanism of Tyrosine Kinase signalling.1. Ligand binds to TK receptor & dimerises.
    2. Dimerization activates TK portion of protein.
    3. Triggers autophosphorylation at tyrosine residues.
    4. Receptor can recognise & activate adaptor proteins.
    5. Activated relay proteins pass the signal within the cell to elicit the response.
  41. 41Explain the MAP Kinase Cascade.1. Autophosphorylation of tyrosine residues --> GRB2 & SOS (adaptor proteins) bind.
    2. GRB-SOS complex activates RAS (G-protein).
    3. RAS activates MAPKKK --> activates MAPKK --> activates MAPK.
    4. MAPK dissociates in nucleus & phosphorylates transcription factors --> stimulates gene transcription.
  42. 42What is Trastuzumab?Monoclonal antibody.
  43. 43Describe the mechanism of Trastuzumab action.targets HER2 Tyrosine Kinase Receptor (found on 25% of breast cancer cells).
    Trastuzumab binds to HER2 --> blocks binding of natural ligand (EDF) & downstream signalling.
  44. 44What is Imatinib & how does it act?Tyrosine kinase inhibitor - Anti-cancer Drug
    Binds to TK domain & deactivates erroneous signal.

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University - Medicine FoM Year 1 (Nutrition & Metabolism) Flashcards on Signal Transduction, created by Jacob Coe on 10/01/2022.
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