Transduction Systems 1 Flashcards
How are enzymes and second messengers involved in signal transduction?
The response involves a sequences of biochemical reactions usually carried out by ENZYMES
the biochemical reactions are linked through SECOND MESSENGER MOLECULES
What is a signal cascade?
the sequence of biochemical reactions that allows a stimulus to be amplified and sometimes expanded to produce multiple different responses
What are the most common second messengers?
- cyclic nucleotides
- calcium ions
- PIP3
What are cyclic nucleotides and what are some examples?
They are a derivative of ATP converted by the enzyme adenosine phosphate which removes two phosphates
examples are cyclic AMP and cyclic GMP
What is PIP3 and what can it be broken down into?
A phospholipid of the cell membrane that is converted by an enzyme into DAG (which stays in the membrane) and IP3 (released into the cell)
What do second messengers do?
Regulate the function of specific cellular effectors - KINASE or PHOSPHOTASE enzymes
In order for a stimulus to produce a response it must take advantage of the signal transduction pathway. How does it do this?
Through 4 primary types of receptors
- receptors linked to ion channels
- receptors coupled to G proteins
- receptors coupled to enzymes
- nuclear receptors
What is an example of a receptor linked to ion channels?
Ligand gated ion channels
What happens when a ligand binds to a receptor linked to an ion channel?
A pore in a membrane opens which increases the permeability of the membrane to Na+ K+ and Cl-
What happens when the movement of ions is increased due to the pore opening?
It affects a cellular response for example post synaptic excitatory or inhibitory response
How does the movement of ions through the opened more affect an ion channel?
Ion channels respond to the change in membrane potential - voltage gated ion channels
What causes the outside of the cell of be normally more positive than the inside?
It is a resting membrane potential due to the fact the Na+/K+ pump puts 3 Na+ out and 1 K+ in
How many subunits does a ligand gated ion channel have?
5 large multimeric protein subunits forms a pore
How fast acting are these channels and what different kinds of ion channels are there?
Very rapid (milliseconds) Cation channels (can't distinguish between K+ and Na+) Chloride channels
What is signal transduction?
The process that allows the cell to convert an extracellular signal into a response
What is depolarisation?
Cell activation by cations
What is hyperpolarisation?
Cell inhibition by anions
What kind of movement is of the ions of these channels?
Passive movement - ill only move in the direction the gradient allows
In what kind of cells are these receptors found and what are some examples?
Fast responding cells e.g. on nerves and muscles where a response is instantaneous
What is an example of a ligand gated ion channel?
Acetylcholine nictonic receptor
An Ach nictonic receptor has 5 subunits, how many of them contain binding sites and what subunits are these?
2 of them and they are alpha subunits
Where does the ligand bind and what does this do? (ANR)
Binds to both the alpha binding sites which opens the pore to allow Na+ ions to rush into the cell which causes muscle contraction
What is tubocurraine?
An antagonist at acetylcholine receptors
What kind of antagonist is tubocurraine?
A competitive, reversible antagonist
What is tubocurraine?
An antagonist at acetylcholine nictotinic receptors
What kind of antagonist is tubocurraine?
A competitive, reversible antagonist of acetylchlone
How can tubocurraine be used in the modern world?
It is used to relax muscle during surgery as it blocks the affect of acetylcholine at nicotinic receptors and therefore causes muscle paralyses
Tubocurraine is reversible; how is its affect overcome?
By increasing the concentration of acetylcholine
To overcome tubocurraine you increase the concentration of acetylcholine; how would you do this?
By inhibition of the enzyme acetylchloineesterase which normally causes breakdown of acetylcholine by hydrolysis of the ester; if you inhibit acetylcholinesterase you then inhibit acetylchloine breakdown which increases the concentration of it allowing it to compete more with tubocurraine and reverse its effects
Acetylcholine nictotinic receptors are an example of cation ion channels; what is an example of a chloride ligand gated ion channel?
GABAa Receptors
What does GABA stand for?
Gamma Amino Butyric Acid (a neurotransmitter)
What happens when the GABAa receptor ion channel is opened?
Cl- ions enter causing hyperpolarisation and cell inhibition
Agonists that act on GABAa receptors therefore cause cell inhibition; what kind of drugs would want to target and activate these receptors?
Drugs that are used as sedatives, tranquillizers and also drugs used to treat seizures (anticonvulsants) such as diazepan
What affect does alcohol have on the GABAa receptors?
It is an allosteric agonist and enhances the ability of the channel
What is the structure of a G-Protein Coupled Receptor?
3 extracellular loops, 3 intracellular loops and 7 transmembrane domains
Name two things about the extraceullar loops of the GPCR
- The loops are often glycosolated
2. They contain two cysteine residues which produce disulphide bonds to stabalise the receptor
GPCR activates a G protein in order to produce a response; what is the structure of a G protein and where is it located?
It is a protein of 3 subunits (a, B, and y) attached to the membrane
Which two of the three subunits of the G protein are closely associated
The b and the y subunits form a complex
What is the function of the G protein subunits?
a contains GDP in its binding site and can activate an intracellular target (i.e. an enzyme) and the b/y complex can also activate an intracellular target (another enzyme)
What are the steps involved in GPCR signalling?
- Agonist binds receptor
- The alpha subunit of the G-protein associates itself with the receptor, it has GDP bound to its active site
- The GDP of the alpha subunits active site is replaced by GTP which activates the subunit
- The GTP bound alpha subunit interacts and activates an enzyme while the b/y complex does the same
- The GTP of the alpha subunit is hydrolysed back to GDP by GTPase and the agonist leaves the receptor - everything returns back to the start
Name 5 functions of the GPCRs?
- sensation
- behaviour
- immune system and inflammation
- metabolism
- autonomic nervous system
Give an example of how GPCRs are used in sensation?
They are found in the retinas of the eye and respond to photons of light called opsins
Give an example of how GPCRs are involved in behaviour?
They can be activated by neurotransmitters e.g. serotonin or dopamine which then lead to certain responds
Give an example of how GPCRs are involved in the immune system?
Chemokine GPCRs are involved in the recruitment of immune cells to certain locations
Give an example of how GPCRs are involved in inflammation?
Histamine GPCRs generate immune responses
Give an example of how GPCRs are involved in metabolism?
GPCRs of the pancreas are used to sense gut hormone or dietary components in order to regulate glucagon and insulin secretion
Give an example of how GPCRs are involved in the autonomic nervous system?
The sympathetic nervous system uses adrenoceptor and the parasympathetic uses muscarinic receptors to mediate their effects
