Metabotropic Receptors and Cell Signaling
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Questions and Answers

What is the primary function of metabotropic receptors?

  • Bind ligands without signal transduction
  • Mediate effects through metabolic processes (correct)
  • Directly open ion channels
  • Act as structural proteins
  • How many transmembrane α-helices do G-protein coupled receptors (GPCRs) typically possess?

  • 7 (correct)
  • 5
  • 9
  • 12
  • What is the role of the third intracellular loop (i3) in GPCRs?

  • It binds ligands directly
  • It varies greatly in length and sequence (correct)
  • It is highly conserved across all receptors
  • It is responsible for receptor dimerization
  • What is a key feature of the structure of metabotropic receptors?

    <p>They include an extracellular N-terminus (C)</p> Signup and view all the answers

    Why is knowledge of cell signalling crucial in biochemistry?

    <p>It helps understand disease processes (C)</p> Signup and view all the answers

    What type of receptors do G-proteins couple to?

    <p>Metabotropic receptors (C)</p> Signup and view all the answers

    What modification near the N-terminus of GPCRs is important for membrane trafficking?

    <p>Glycosylation (B)</p> Signup and view all the answers

    What is the significance of the 865 currently known GPCRs?

    <p>They represent the largest family of receptors (A)</p> Signup and view all the answers

    What effect does disruption of disulphide bonds have on ligand binding?

    <p>Decreases ligand binding capacity (D)</p> Signup and view all the answers

    Replacing cysteine in the C-terminal domain affects which aspect of receptor function?

    <p>G-protein coupling (A)</p> Signup and view all the answers

    Which G-proteins are thought to activate processes linked to different effector molecules?

    <p>Gs, Gi, and Gq (B)</p> Signup and view all the answers

    What initiates the signalling cascade in the fight or flight response?

    <p>Release of adrenaline (C)</p> Signup and view all the answers

    What is the main consequence of the cholera toxin's action on G-protein signaling?

    <p>Permanent activation of adenylate cyclase (D)</p> Signup and view all the answers

    Excess chloride transport into the lumen due to cholera toxin leads to what physiological effect?

    <p>Dehydration due to water loss (C)</p> Signup and view all the answers

    Which pathway is primarily activated by the binding of adrenaline to its receptor?

    <p>cAMP signaling pathway (B)</p> Signup and view all the answers

    What type of protein is produced by the cholera-causing organism Vibrio cholera?

    <p>Hexameric protein (C)</p> Signup and view all the answers

    Flashcards

    Metabotropic Receptors

    Receptors triggering a series of metabolic events, often involving enzyme activation to transduce the signal. They are key players in cellular communication and response.

    G-Protein Coupled Receptors (GPCRs)

    Receptors with seven transmembrane domains that are coupled to G proteins. They represent a large and diverse family of receptors with critical roles in various cellular processes.

    Extracellular N-terminus of GPCRs

    The region extending outside the cell membrane. Often houses the ligand-binding site and plays a crucial role in receptor activation.

    Intracellular C-terminus of GPCRs

    The region extending inside the cell membrane. It interacts with intracellular signaling molecules like G proteins and is vital for initiating the signal transduction pathway.

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    Third Intracellular Loop (i3) of GPCRs

    A highly variable region within the GPCR structure. Its diverse sequence and length contribute to the receptor's specificity and interaction with G proteins.

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    G-Protein

    A molecular switch responsible for relaying signals from activated GPCRs to downstream effectors. They are trimeric proteins with a structure comprising alpha, beta, and gamma subunits.

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    Signal Transduction

    The process by which a signal is transmitted from the outside of the cell to the inside, ultimately leading to a cellular response. Involves a cascade of events starting with receptor activation and culminating in cellular changes.

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    Glycosylation

    A modification process that involves the addition of a carbohydrate molecule to a protein. This modification plays a crucial role in protein folding, stability, and functionality.

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    Ligand Binding Capacity

    The ability of a receptor to bind a ligand, measured by the number of ligand molecules that can bind to the receptor.

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    Disulfide Bond

    A type of covalent bond formed between two cysteine amino acid residues in a protein. This bond is important in stabilizing the protein's structure and function.

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    G Protein-Coupled Receptor (GPCR)

    A type of G protein-coupled receptor that is involved in a variety of signaling pathways, including those involved in the fight-or-flight response.

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    Gs Proteins

    A family of G proteins that activate adenylyl cyclase, an enzyme responsible for producing cyclic AMP (cAMP).

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    Adrenaline

    A hormone produced by the adrenal gland that is involved in the fight-or-flight response. It binds to G protein-coupled receptors on muscle and liver cells, triggering a cascade of events that lead to increased glucose release and heart and breathing rates.

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    Cholera Toxin

    A toxin produced by Vibrio cholerae bacterium that causes severe diarrhoea and dehydration. The toxin disrupts intestinal epithelial cells by modifying G proteins, preventing the inactivation of adenylyl cyclase and leading to excessive cAMP production.

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    Cyclic AMP (cAMP)

    A cyclic nucleotide that acts as a second messenger in many signaling pathways. It is involved in a variety of cellular processes, including glucose metabolism, smooth muscle relaxation, and memory formation.

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    Study Notes

    Metabotropic Receptors

    • Metabotropic receptors are slower but have a longer-lasting effect than ionotropic receptors.
    • They utilize a series of metabolic processes, often involving enzyme activation, to transduce signals.
    • An example of this process is the fight-or-flight response.

    Learning Outcomes

    • Explain the principles of cell signaling and signal transduction.
    • Define metabotropic receptors and G-protein-coupled receptors.
    • Explain the structure of G-protein-coupled receptors and how this impacts their activity.
    • Explain the actions of a G-protein when a ligand binds.
    • Explain GPCR signaling transduction.

    Cell Signaling and Signal Transduction

    • Cell signaling is a crucial aspect of modern biochemistry and cell biology.
    • It's essential for cell-cell communication and coordinated cellular function in all organisms.
    • Understanding cell signaling is crucial for comprehending various diseases, like cancer and diabetes.

    Types of Receptors

    • Receptors can be broadly categorized into ligand-gated ion channels, G-protein-coupled receptors, kinase-linked receptors, and nuclear receptors.
    • Each type of receptor mediates signals differently, impacting cellular responses in various ways.
    • Receptors have diverse time scales for their effects, ranging from milliseconds to hours.

    Receptor Names

    • Metabotropic receptors mediate their effects by activating a series of metabolic processes, usually involving enzyme activation to transduce the signal.
    • 7-transmembrane G-protein-coupled receptors are a specific type and are characterized by their structure and mechanism of transducing chemical signals.

    Type 2: G-protein-coupled Receptors

    • G protein-coupled receptors (GPCRs) are transmembrane receptors, typically spanning the cell membrane seven times.
    • They are composed of 400-500 polypeptide chains.
    • GPCRs employ G proteins to mediate their interactions with intracellular effector systems.
    • This receptor family is one of the largest and is a common therapeutic target for various drugs.

    Structure of GPCRs

    • GPCRs have seven transmembrane α-helices that are largely conserved.
    • The extracellular N-terminus and intracellular C-terminus exhibit variation in length and sequence.
    • The third intracellular loop is highly variable.

    Modifications to GPCR Structure

    • Glycosylation, with carbohydrates bonded near the N-terminus, plays a critical role in membrane traffic and insertion, but not in ligand binding.

    Ligand Binding Capacity

    • Disulfide bonds connect cysteines in loops E2 and E3.
    • Disruption of these bonds can reduce ligand binding capacity.

    Effectiveness of Cellular Response

    • Cysteine residues in the C-terminal domain stabilize receptor-membrane interactions.
    • Replacing these cysteines doesn't affect ligand binding but may reduce G-protein coupling.

    Protein Coupling

    • Different G protein subtypes exist.
    • The α-subunit largely determines the subtype (e.g., G₂, G₁, Gq, or G₁₃).

    Type 2: G protein-coupled Receptors

    • Different G proteins activate different effector molecules, like enzymes and ion channels.
    • Examples include adenylyl cyclase and phospholipase C.
    • Alpha subunits define the subtypes (Gs, G₁, Gq, or G₁₃).

    Signaling Pathway Involving Second Messengers IP₃ and Ca²⁺

    • Signaling pathways trigger responses like changes in cell metabolism, activation of gene activity, or opening or closure of ion channels.
    • Second messengers like IP₃ and Ca²⁺ are involved in these processes.

    Fight-or-Flight Pathway

    • Adrenaline, a hormone released by the adrenal gland, plays a key role in the fight-or-flight response.

    • It travels through the bloodstream to muscle and liver cells and binds to G protein-coupled receptors.

    • The binding triggers a cascade of events that result in glucose release to prepare the body for action.

    Disease Associated with G-proteins (Cholera)

    • Vibrio cholera toxin affects intestinal epithelial cells.
    • Beta subunits of the toxin attach to the cells, and alpha subunits activate adenylyl cyclase.
    • High cAMP levels lead to chloride transport into the lumen and sodium absorption.
    • These processes result in water loss.

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    Description

    This quiz explores the principles of cell signaling and the role of metabotropic receptors in signal transduction. You'll learn about G-protein-coupled receptors, their structure, and their impact on cellular functions. Understanding these concepts is vital for grasping their implications in various diseases.

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