chapter 23 Signal Transduction Mechanisms: II. Messengers and Receptors Flashcards
What does the study of “Signal Transduction Mechanisms: II. Messengers and Receptors” focus on?
It explores how cells respond to nonneuronal signals
How do cells produce signals?
Cells produce signals by displaying molecules on their surfaces or by releasing chemical signals
What is the role of chemical signaling in multicellular organisms?
To regulate and coordinate the various activities of cells and tissues.
How do multicellular organisms control specialized cell activities?
Through the release of chemical messengers
What are the two main classifications of signaling molecules based on the distance from the production site to the target?
- Endocrine signals: Produced far from the target tissues and reach them via the circulatory system.
- Paracrine signals: Diffusible and act over a short range.
What are juxtacrine and autocrine signals?
Juxtacrine signals: Require physical contact between sending and receiving cells.
Autocrine signals: Act on the same cell that produces them.
In the context of cell-to-cell signaling, what is the importance of hormones and local mediators?
They facilitate communication between cells by acting as signaling molecules
What is a ligand, and where can it bind?
A ligand is a messenger molecule that binds to a receptor, either on the surface of the target cell or inside it
How do ligands bind to receptors?
Ligands bind to receptors at a closely fitting binding site (or binding pocket) where the necessary amino acid side chains of the receptor form chemical bonds with the messenger.
What does “The Overall Flow of Information During Cell Signaling” refer to?
The process by which information is transmitted from a ligand binding to its receptor, leading to cellular responses.
What is the first step in cell-cell signaling?
Ligand binding to a receptor.
What are second messengers in signal transduction?
Molecules or ions produced within the cell following ligand binding, initiating further signaling events.
What is signal transduction?
The ability of a cell to respond to ligand-receptor binding by altering its behavior or gene expression.
How does ligand binding alter receptors?
It can change the receptor’s conformation, cause receptors to cluster together, or both, triggering signal transduction events.
What does “preprogrammed” mean in the context of cellular responses?
It refers to a cell’s repertoire of functions, some of which are unused until triggered by a specific signal.
How does receptor-ligand binding resemble enzyme-substrate interaction?
A receptor binds to a ligand in a manner similar to an enzyme binding its substrate, and the receptor is considered “occupied” when bound.
What happens as ligand concentration increases?
Saturation is reached when most receptors are occupied by the ligand.
What is receptor affinity?
The relationship between ligand concentration in solution and the number of receptors occupied.
Define the dissociation constant (Kd).
The concentration of free ligand required to occupy half of the available receptors.
How is receptor affinity related to Kd?
High receptor affinity corresponds to a low Kd, and vice versa.
What is the equilibrium constant (Ka) formula?
Ka=[HR] / [H][R], where HR is the hormone-receptor complex, H is the hormone concentration, and R is the receptor concentration.
How is the dissociation constant (Kd) calculated?
Kd = [H][R] / [HR]
What is fractional occupancy in receptor-ligand binding?
The fraction of receptors occupied by a ligand, given by
[𝐻𝑅] / [𝑅] + [𝐻𝑅]
What is the fractional occupancy when ligand concentration ([H]) is zero?
the fractional occupancy is 0
What happens to fractional occupancy when ligand concentration greatly exceeds Kd?
fractional occupancy approaches 1
What is the relationship between Kd and receptor saturation?
When the receptor is half saturated, the ligand concentration ([H]1/2) equals Kd
How can Kd for a simple receptor-ligand system be visualized?
Through concentration dependence of ligand binding and reciprocal plots, such as the Scatchard equation.
Why is measuring real-world Kd values challenging?
Because it is technically difficult and often done indirectly.
What are agonists and their function?
Agonists are drugs that activate the receptor they bind to.
What are antagonists and their function?
Antagonists bind receptors without triggering a change and prevent natural messengers from activating the receptor.
What are two common ways cells shut down receptor signaling?
- Reducing the amount of free ligand.
- Reducing receptor sensitivity or receptor numbers.
What is receptor desensitization?
A process where prolonged receptor occupation causes the cell to adapt and no longer respond to the ligand.
How can cells reduce receptor activity biochemically?
By adding or removing phosphate groups to/from amino acids, altering receptor affinity.
Provide an example of signal amplification.
A single epinephrine ligand binding to a liver cell receptor can release hundreds of millions of glucose molecules from glycogen.
What does signal transduction pathway amplification achieve?
It amplifies the cellular response to an external signal.
How do cell-cell signals act through receptors and signal transduction pathways?
Cells use a limited number of basic signaling pathways and receptors to process signals.
What types of ligands bind to transmembrane receptors?
Hydrophilic ligands, which include proteins, small peptides, amino acids and their derivatives, and nucleotides or nucleosides.
Where do hydrophobic ligands act, and what is their function?
Hydrophobic ligands bind to receptors in the cytosol and can enter the nucleus to regulate transcription of specific genes.
What are some examples of hydrophobic ligands?
Steroid hormones and retinoids.
What are the key types of signaling pathways for hydrophilic ligands?
- Ligand-gated ion channels.
- G protein−coupled receptors relying on GTP hydrolysis.
- Receptors activating cytosolic enzymes like protein kinases.
What are G protein−coupled receptors (GPCRs)?
Receptors that, upon ligand binding, change conformation to activate a specific G protein (guanine-nucleotide binding protein).
How do GPCRs act via hydrolysis of GTP?
An activated G protein binds a target protein (enzyme or channel protein), altering its activity.
Give examples of G protein−coupled receptor targets.
Olfactory receptors, β-adrenergic receptors, and hormone receptors, including clinically important opioid receptors.
Describe the structure of GPCRs.
GPCRs have seven transmembrane α helices connected by cytosolic or extracellular loops. The extracellular portion contains a unique messenger-binding site.
How is the cytosolic portion of a GPCR significant?
It allows the receptor to interact with specific types of G proteins.
How are GPCRs regulated through phosphorylation?
G protein−coupled receptor kinases (GRKs) phosphorylate amino acids in the receptor’s cytosolic domain, targeting activated receptors.
How is Protein Kinase A (PKA) involved in GPCR signaling?
PKA is activated by G protein-mediated signaling and can phosphorylate amino acids on the receptor, inhibiting it. This serves as an example of negative feedback during cell signaling.
How do G proteins act in signal transduction?
G proteins act as molecular switches, with “on” and “off” states depending on whether they are bound to guanosine triphosphate (GTP) or guanosine diphosphate (GDP).
What are the two types of G proteins, and what are their roles?
- Heterotrimeric G proteins: Mediate signal transduction through GPCRs and have Gα, Gβ, and Gγ subunits.
- Monomeric G proteins: Involved in smaller signaling pathways.
What happens when Gα binds to GTP?
Gα detaches from the Gβγ subunits and initiates signal transduction, depending on the G protein and cell type.
What is the function of Gβγ subunits in G protein signaling?
Gβγ subunits associate with GPCRs and can initiate signaling events, including opening ion channels or activating other proteins.
Describe the steps in the activation of G proteins.
- Gα binds to GDP and detaches from Gβγ.
- Gα binds to GTP and activates signal transduction by binding to target enzymes or proteins.
- Gα hydrolyzes GTP to GDP, reassociating with Gβγ, shutting down the signaling pathway.
What regulates the activity of G proteins?
G protein activity is enhanced by regulators of G protein signaling (RGS) proteins and GTPase-activating proteins (GAPs), which promote GTP hydrolysis.
What is the primary function of G proteins in signal transduction?
To release or form second messengers, which amplify the cellular response.
How do the α and βγ subunits of G proteins engage in signaling?
The α subunits interact with enzymes like adenylyl cyclase and phospholipase C, while βγ subunits can activate other proteins, such as G protein-coupled receptor kinases.
What happens when acetylcholine binds the muscarinic acetylcholine receptor?
The βγ subunits of the G protein cause the opening of potassium channels in the membrane, which close again when acetylcholine is no longer present.
What are second messengers in G protein-mediated signaling?
Second messengers are molecules like cyclic AMP (cAMP) and calcium ions, which are crucial in mediating signal transduction.
How is cyclic AMP (cAMP) formed?
cAMP is formed from cytosolic ATP by the enzyme adenylyl cyclase, which is activated when bound to GTP-Gsα.
What activates adenylyl cyclase to produce cAMP?
Adenylyl cyclase is activated when GTP-Gsα binds to it after receptor-ligand binding, causing the release of Gsβγ.
How long do G proteins remain active, and why is this important?
G proteins remain active for a very short time, which allows them to quickly respond to changing conditions in the cell.
What happens when Gsα becomes inactive?
When Gsα becomes inactive, adenylyl cyclase stops producing cAMP, and the remaining cAMP is degraded by phosphodiesterase.
What is the main function of cAMP in signal transduction?
cAMP regulates protein kinase A (PKA) by separating its regulatory and catalytic subunits, which allows PKA to phosphorylate proteins.
What does PKA phosphorylate, and what is the energy source for this process?
PKA phosphorylates proteins on serine or threonine residues using ATP as the phosphate source.
How does an increase in cAMP concentration affect cells?
The effects of increased cAMP concentration vary between different cell types, affecting various cellular functions.
What disease is caused by the disruption of G protein signaling due to cholera toxin?
Cholera is caused by cholera toxin, which modifies Gs so that it cannot hydrolyze GTP, disrupting salt and fluid secretion in the intestine and leading to dehydration.
How does the pertussis toxin affect G protein signaling in whooping cough?
Pertussis toxin modifies Gi so it cannot inhibit adenylyl cyclase, causing fluid accumulation in the lungs and the persistent cough characteristic of whooping cough.
What is the role of inositol-1,4,5-trisphosphate (IP3) in signal transduction?
IP3 acts as a second messenger, generated from PIP2 when phospholipase C is activated, and plays a key role in the release of calcium ions.
How are inositol trisphosphate (IP3) and diacylglycerol (DAG) produced?
They are produced when phospholipase C cleaves PIP2 (phosphatidylinositol-4,5-bisphosphate), generating both IP3 and DAG.
What are some cell functions regulated by inositol trisphosphate (IP3) and diacylglycerol (DAG)?
Functions include cell growth, regulation of ion channels, changes in the cytoskeleton, increases in cellular pH, and effects on secretion of proteins and other substances.
