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Questions and Answers
What is the primary function of the transduction stage in signal transduction?
What is the primary function of the transduction stage in signal transduction?
What type of receptor recognizes signaling molecules in the cytosol?
What type of receptor recognizes signaling molecules in the cytosol?
What is the outcome of an agonist binding to a receptor?
What is the outcome of an agonist binding to a receptor?
What is the role of G proteins in G protein-coupled receptor signaling?
What is the role of G proteins in G protein-coupled receptor signaling?
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What is the final stage of signal transduction?
What is the final stage of signal transduction?
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What is the term for the binding of a signaling molecule to its receptor?
What is the term for the binding of a signaling molecule to its receptor?
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What is the primary function of parathyroid hormone in the body?
What is the primary function of parathyroid hormone in the body?
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What is the significance of calcium in the body?
What is the significance of calcium in the body?
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What is the characteristic of hypocalcaemia?
What is the characteristic of hypocalcaemia?
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Where is the largest concentration of calcium found in cells?
Where is the largest concentration of calcium found in cells?
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What is the function of PMCA in cells?
What is the function of PMCA in cells?
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How do calcium sinks work in cells?
How do calcium sinks work in cells?
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What is the significance of calcium in skeletal mineralization?
What is the significance of calcium in skeletal mineralization?
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What percentage of calcium in the body is found in the bones of the skeleton?
What percentage of calcium in the body is found in the bones of the skeleton?
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What is the function of an antagonist in a GPCR signalling pathway?
What is the function of an antagonist in a GPCR signalling pathway?
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What is the structure of the receptor part of GPCRs?
What is the structure of the receptor part of GPCRs?
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What is the function of Gα in GPCR signalling pathways?
What is the function of Gα in GPCR signalling pathways?
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What is the outcome of activation of a Gs active alpha subunit?
What is the outcome of activation of a Gs active alpha subunit?
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What is the function of adenyl cyclase in GPCR signalling pathways?
What is the function of adenyl cyclase in GPCR signalling pathways?
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What is the outcome of activation of a Gq active alpha subunit?
What is the outcome of activation of a Gq active alpha subunit?
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What is the function of signal amplification in GPCR signalling pathways?
What is the function of signal amplification in GPCR signalling pathways?
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What is the outcome of activation of a Gi active alpha subunit?
What is the outcome of activation of a Gi active alpha subunit?
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What is the structure of G-proteins in GPCR signalling pathways?
What is the structure of G-proteins in GPCR signalling pathways?
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What is the function of the beta-gamma subunit in GPCR signalling pathways?
What is the function of the beta-gamma subunit in GPCR signalling pathways?
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What is the primary function of NCX in the cell?
What is the primary function of NCX in the cell?
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What is the energy requirement for SERCA to function?
What is the energy requirement for SERCA to function?
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Which of the following channels is opened by ligand binding?
Which of the following channels is opened by ligand binding?
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What is the number of binding sites for calcium in calmodulin?
What is the number of binding sites for calcium in calmodulin?
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What is the primary mechanism of action of calcium channel blockers?
What is the primary mechanism of action of calcium channel blockers?
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Which of the following is NOT a mechanism that increases intracellular Ca2+?
Which of the following is NOT a mechanism that increases intracellular Ca2+?
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What is the primary effect of calcium channel blockers on blood vessels?
What is the primary effect of calcium channel blockers on blood vessels?
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What is the role of calmodulin in the cell?
What is the role of calmodulin in the cell?
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Study Notes
Signal Transduction Pathways
-
The 4 sections of signal transduction are:
- Signals: ligand
- Receptors: recognise signalling molecules, cause a conformation change
- Transduction: signalling cascade with secondary messengers
- Response: regulation of cellular activities
-
Signalling molecules are recognised by:
- Membrane receptors (such as GPCRs)
- Intracellular receptors
G-Protein Coupled Receptors (GPCRs)
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GPCRs are cell receptors linked to a G protein on the plasma membrane
-
GPCRs work in the plasma membrane by:
- Ligand binds to receptor on plasma membrane
- Activates G-protein
- G-protein activates effector
- Generates secondary messengers
-
Structure of GPCRs:
- Membrane receptors (except rhodopsin)
- Single α-helix polypeptide chain
- 7-Transmembrane regions (H)
- Extracellular (E) and cytosolic regions (C)
Agonists and Antagonists
- Agonists: bind to the receptor and activate it, leading to intracellular signal transduction events
- Antagonists: bind to the receptor, but do not activate it, blocking the effects of agonists at the receptor
G-Protein Structure
- G-proteins: Guanine nucleotide (GTP) binding proteins
- G-proteins are heterotrimeric, made up of 3 subunits: α, β, and γ
- Gα: carries the binding site for the nucleotide (GDP, GTP)
- Gβ: beta subunit
- Gγ: gamma subunit
GPCR Function
- GPCR function:
- Ligand binds to receptor at the 7-transmembrane region
- Nucleotide exchange at the α subunit, GDP → GTP
- Activation occurs, α subunit dissociates
- Subunits carry on signal transduction and amplification
- After binding to receptor is finished, signalling quantity decreases
- α unit is favoured back to its resting conformational state (GTP → GDP)
Active Alpha Subunit
- The 4 names of the active alpha subunit are:
- (names not specified)
- These names recognise the secondary messengers they cascade
Outcomes of Active Alpha Subunit
- Activation of Gs or Gi active alpha subunit:
- Adenylyl cyclase/cAMP signalling activity
- Activation of G12/13 active alpha subunit:
- Small GTPase families
- Activation of Gq active alpha subunit:
- Activates phospholipase C/IP3/DAG Signalling pathway (target enzyme)
Beta-Gamma Subunit
- The 3 names of the active beta-gamma subunit are:
- (names not specified)
Adenyl Cyclase
- Adenyl cyclase is an enzyme that changes bonds in ATP molecule (linear → Cyclic structure)
- Produces cAMP (secondary messenger) (can be activated/inhibited by different ligands)
Signal Amplification
- Signal amplification: 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
Calcium Regulation
- Parathyroid hormone regulates Ca levels
- Calcium is an essential element in the body:
- Important role in skeletal mineralisation
- >99% of calcium in the body is found in the bones of the skeleton
- Hypocalcaemia: calcium levels are < 8.5 mg/dL
- The largest concentration of calcium is found in the Endoplasmic Reticulum
Calcium Sinks
- Calcium sinks work by:
- Cytoplasm/cytosol acts as a sink
- Calcium flows from the extracellular matrix
- Calcium flows through the cytoplasm
- Calcium is stored in the SR/ER (smooth endoplasmic reticulum)
Calcium Transport
- PMCA (Ca2+ transport, ATPase):
- Transporter that requires ATP, releases calcium from cytosol to extracellular matrix
- Maintains low cytosolic Ca2+
- NCX (Na+/Ca2+ exchanger):
- Transporter mechanism from cytosol to extracellular matrix
- No need for ATP
- Maintains low cytosolic Ca2+
- SERCA:
- Transporter
- ATP-dependent
- Fills the smooth endoplasmic reticulum's Ca2+ storage from Cystolic Ca2+
Mechanisms of Increasing Intracellular Ca2+
- The 4 mechanisms/channels that increase intracellular Ca2+ are:
- 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
Calmodulin
- Calmodulin is a protein that binds to calcium
- Calmodulin has 4 binding sites for calcium
- Calmodulin will move and activate other proteins
Clinical Use of Calcium Channel Blockers
- Calcium channel blockers are medications used to lower blood pressure
- They block calcium influx, allowing blood vessels to relax and open
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Description
Understand the mechanisms of signal transduction, including the 4 sections: signals, receptors, transduction, and response. Learn how signals are transmitted and regulated within cells.