deck_614136 Flashcards
What can signalling occur between?What are three types of chemical signal classification?
Between secreted molecules and between plasma membrane bound molecules Endocrine - HormoneSynaptic - NeutransmissionParacrine - Chemical Mediators
What is hormonal signalling?
Signalling between cells in different tissues via the circulation
What kind of signalling do neurotransmitters do?
Signalling at specialised cell junctions in the nervous system at synapses
Define paracrine signalling
Signalling where the target tissue is close to the cell releasing the hormone xc- local chemical mediators
Define ligand
Any small molecule that binds specifically to a receptor site
What kind of action does an agonist ligand bring about?
Agonist activate receptors
What action does an antagonist ligand bring about?
In binds with a receptor without causing activation– opposes the agonist
What is the name for an agonist that stimulates a receptor but does not elicit a maximum cell response?
Partial agonist
Define receptorWhat occurs when the receptor is in an unbound state
A molecule that recognises specifically a ligand or family of ligands. In response to ligand binding. It brings about regulation of a cellular process Unbound state = functionally silent
What does the binding of adrenaline to a B-adrenergic receptor activate?
It activates adenylyl cyclase which activates a cascade of events inside the cell.
Which has a higher affinity: ligand binding at a receptor or substrates and allosteric regulators to enzyme sites?
Ligand binding at receptor sites
Give some examples of the roles that receptors have? (8)
• Signalling by hormones/local chemical mediators• Neurotransmission• Cellular delivery• Control of gene expression• Cell adhesion• Modulation of the immune response• Sorting of intracellular proteins• Release of intracellular calcium stores
How are receptors classified?
By which signal molecule they recognise before being subclassed in to their affinity for certain antagonistse.g. ACh receptors can be nicotinic or muscarinic but both will bind to nicotine and muscarine.
What are the differences between receptors and acceptors?
Receptors – are silent at rest and agonist binding stimulates a biological responseAcceptors – can operate in absence of ligand.
How has evolution solved the problem of transducing extracellular into intracellular signals?
The receptor and the effector molecules are on separate proteins but are coupled by a transducing protein.
What are the four methods of signal transduction?What are the relative speeds of change for each process?
- Membrane-bound receptors with integral ion channels2. Membrane-bound receptors with integral enzyme activity3. Membrane-bound receptors which couple to effectors through transducing proteins4. Intracellular receptorsFast to slow – 1 to 4
What is an acceptor?
A molecule which can carry out its basic function without the binding of a ligand
Give some examples of membrane-bound receptors with integral ion channels
• Nicotinic acetylcholine receptor (nAChR)• Gamma amino butyric acid (GABA) receptor • Glycine receptor- gated chloride channel• Glutamate receptors - Gated Ca2+ entry• Inositol 1,4,5-trisphosphate (IP3) receptor - gated release of Ca2+ from the ER
Why is signal transduction necessary?
Hydrophillic signal molecules cannot pass through the cell membrane – must bind to an extracellular receptor to transmit the signal into the cell. All signal need a receptor in order for the cell to recognise a specific signal and be able to coordinate a response.
Describe ligand gated ion channels and the method of signal transduction
Agonist binding to a ligand gated channel causes a conformational change in the receptor, opening the channel and allowing the flow of ions down and electrochemical gradient, stimulating an electrical response in the cell.
What is the classical subunit structure of a logan gated ion channel and give an example of one of these receptors.
pentameric subunit structures with four transmembrane domains. The M2 domain lines the channel pore. – nicotinic ACh receptor
What type of residues are present in nACh receptors which give it selectivity?
Acidic residues which are negative therefore give the pore cationic attraction
What other type of ligand gated ion channels can you get?
Non-classical ligand gated ion channelse.g ATP sensitive K+ channel, Ryanodine receptors and P2x purinoceptors
Descibe the series of events that occur when an agonist binds with membrane bound receptors with integral enzyme activity
Agonist binding to these receptors causes a conformational change, which activates an intrinsic enzyme activity which is contained within the protein structure of the receptor
Give some examples of membrane bound receptors with integral enzyme activity
- Atrial natriuretic peptide receptros which is coupled to guanylyl cyclase2. Insulin receptors – tyrosine kinase3. Epidermal growth factor– tyrosine kinase4. Platelet derived growth factor – tyrosine kinase
What happens when an agonist binds to a tyrosine kinase linked receptor?
Protein kinase activated whic autophosphorylate tyrosine residues on the receptors. They are the recognised by other transducing proteinsor enzymes with phosphotyrosine recognition sites (Src-homology-2 domains)This allosterically activates effector enzymes and transduces the message into an intracellular chemical event.
What is the most common mechanism for transducing signals?
Using membrane-bound receptors that signalthrough transducing proteins– Seven transmembrane domain (7TMD) receptors
What are membrane bounds receptors that signal throught ransducing proteins also called?
G-protein coupled receptor family
What type of effectors are present in the G-protein coupled receptor family?
enzymes (adenylyl cyclase)ion channels
Give a couple of examples of signalling molecules that have he seven transmembrane structure
muscarinic ACh receptorsDopamine receptorslight, smell and taste receptorsB-adrenoceptors – adrenaline binding
How do G-proteins work?
Receptor binding results in a conformational change which activates GDP/GTP exchange in GTP-binding regulatory proteins, which transduce the message on to an enzyme or channel in the membrane. The subunits then dissociates and GTP binding to an enzyme or channel and activates it.
What do the different G-proteins do?
Gs = stimulatoryGi = inhibitory
What are the different enzymes that can be activated by G-proteins?
Adenylyl cyclase –> convert ATP to cAMPIon channels e.g. K+ or Ca2+ channels
When do intracellular responses take place?
When there is a hydrophobic ligand (steroid hormones) which can bind to nucleic receptors or monomeric receptors in the cytoplasm.
How are intracellular receptors stabilised in the cell?
By association with heat shock or chaperone proteins.
How are the intracellular signal activated?
The DNA binding domain is blocked by an inhibitory protein. Hormone binding causes a conformational change, which exposes the binding site. Gene transcription is changed.
What is a particular characteristic of intracellular receptors?
They have a very similar structure
Describe integrated signalling
Occurs when separate G-protein coupled receptirs act simultaneaously to stimulate and inhibit the effector. The two inputs combine to produce a measured effort.
What is amplification?
The process by which the concentration of a substrate molecule increases exponentially.– One active ligand can stimulate 4 G-proteins– Activation increases exponentiallyA single receptor can cause the modification of hundreds or thousands of substrate molecules.
What can the binding of a molecule to a receptor do?
Can activate or inhibit actions inside the cell e.g. B-adrenoceptors in the heart increase the rate while ACh muscarinic receptors decrease the ratehepatocytes – insulin stimulates synthesis of glycogen and glucagon stimulate glycogen breakdown
