Biochem

    Cards (17)

    • Cell signalling
      The process by which cells communicate with each other and respond to their environment
    • Types of cell signalling
      • Intercellular signalling
      • Intracellular signalling
    • Types of ligands
      • Low molecular weight organic compounds
      • Peptides and proteins
      • Lipids
      • Sugars
      • Gases
    • Receptor
      • The binding site (usually a protein) for a ligand and often the site of signal transduction
    • Signal transduction
      Converting one signal type to another
    • Second messenger

      An intracellular molecule generated in response to receptor activation by a ligand (the "first messenger") that activates an effector
    • Effector
      An enzyme that responds to a signal e.g. to a second messenger
    • Cell signalling is used to co-ordinate body processes, respond to specific events, and regulate body functions
    • Types of intercellular signalling
      • Endocrine
      • Paracrine
      • Autocrine
      • Contact-dependant
      • Synaptic
      • Gap junctions
      1. protein coupled receptors (GPCRs)

      • Very common receptor type that binds many hormones and neurotransmitters
      • One of the most common drug targets (1/3 drugs target GPCRs)
      • Passes across the plasma membrane seven times (7 α helices)
      • Activates G-proteins on the intracellular side of the membrane
      1. protein
      • Regulated by binding of GTP
      • Comprises three different subunits: α, β, γ
      • There are different isoforms (genes) for each of these subunits, and they activate different intracellular signalling pathways (effectors)
      1. protein signalling
      1. Receptor acts as guanine nucleotide exchange factor (GEF)
      2. GTPase activating protein (GAP) hydrolyses GTP to GDP
      3. Receptor can be desensitized and downregulated
    • Intracellular signalling: cAMP pathway
      1. Adenylyl cyclase (ACy) converts ATP to cAMP
      2. cAMP activates Protein Kinase A (PKA)
      3. PKA phosphorylates substrates
      4. Phosphodiesterase (PDE) degrades cAMP to AMP
    • NO (nitric oxide) acts locally and has a short half-life
    • Nuclear receptor signalling
      Lipid soluble signalling molecules penetrate the cell membrane and bind to intracellular receptors (typically transcription factors) to initiate changes in gene expression
    • Nuclear receptor ligands
      • Steroids
      • Thyroid hormones
      • Retinoids
    • Nuclear receptors
      • Act as homo or hetero dimers
      • Steroid receptors act as homodimers and are found in the cytoplasm, activated upon binding ligand and transfer to the nucleus
      • Vitamin D, retinoid & thyroid hormone receptors act as heterodimers, are located in the nucleus and repress gene expression in absence of ligand
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