IB Biology HLChemical SignallingPaper 1 & 2~14 min read
Transmembrane Receptors
Three receptors, three completely different tricks. One opens a hole in the membrane. One flips a molecular switch. One tags itself with phosphate and hands the job to somebody else. All three start the same way: a ligand binds outside.
📚 What you need to know
Acetylcholine (ACh) is a key neurotransmitter; synapses using it are cholinergic synapses.
ACh binds to ligand-gated sodium ion channels, which are specialised transmembrane receptors.
Binding causes a shape change, the channel opens, and Na+ diffuses into the cytoplasm, reversing the charge across the postsynaptic membrane.
ACh is broken down by acetylcholinesterase to prevent continued stimulation; the products are reabsorbed and recycled.
A G-protein-coupled receptor (GPCR) activates a G-protein, which acts as a switch bound to either GTP (active) or GDP (inactive).
On activation, GTP replaces GDP and the G-protein splits into a GTP-bound alpha subunit and a beta-gamma dimer, which act on enzymes and ion channels.
Receptor tyrosine kinases (RTKs) become phosphorylated using phosphate from ATP and assemble relay proteins; one RTK can trigger several pathways at once.
Insulin binds an RTK, triggering vesicles carrying glucose transporter proteins to fuse with the membrane, raising permeability to glucose.
Acetylcholine and membrane potential
Membrane potential is the voltage across a membrane. Acetylcholine can bring about a change in it — it can reverse the charge across a nerve cell membrane. Here is how.
🧩 At a cholinergic synapse
A nerve impulse arriving at the presynaptic membrane stimulates release of ACh into the synaptic cleft.
ACh molecules diffuse across the cleft and temporarily bind to ligand-gated sodium ion channels in the postsynaptic membrane. These channels are specialised transmembrane receptors.
This causes a shape change in the channel, which opens, allowing positively charged sodium ions (Na+) to diffuse down a gradient into the cytoplasm.
The sodium ions reverse the charge across the postsynaptic membrane, initiating a new nerve impulse.
ACh is broken down by acetylcholinesterase, preventing continued stimulation.
The products are absorbed back into the presynaptic membrane, recycled and packaged into vesicles for the next action potential.
Look at the charges on the left and right of the membrane. Where the channel is open they have swapped over — that reversal is the new nerve impulse.
Notice how short this pathway is. There is no second messenger, no cascade — the receptor is the ion channel. That is exactly why synaptic transmission is measured in milliseconds while a hormone response takes minutes.
G-protein-coupled receptors
A G-protein-coupled receptor (GPCR) is a transmembrane receptor protein responsible for activating a special intracellular protein called a G-protein, which then initiates changes inside the cell. GPCRs are the largest and most diverse group of membrane receptors in eukaryotes.
G-proteins bind to either GTP or GDP, and act as a switch that is turned on or off by signals at the membrane surface:
GTP = guanine triphosphate — active G-protein
GDP = guanosine diphosphate — inactive G-protein
These molecules are very similar to ATP, but contain guanine rather than adenine
Inactive G-proteins are attached to the internal side of a GPCR, bound to GDP.
The subunits are the messengers here. Once they break away they can interact with other membrane proteins and cause the release of second messengers.
🧩 Activating a G-protein
A non-steroid ligand binds to the GPCR on the outside of the cell.
A conformational change occurs, which activates the attached G-protein.
GTP replaces GDP, and the G-protein dissociates from the GPCR in two parts: a GTP-bound alpha subunit and a beta-gamma dimer.
These subunits interact with other membrane proteins and can cause the release of second messengers. Their targets include enzymes and ion channels.
G-proteins return to the inactive state when GTP is hydrolysed to GDP, and they associate with the GPCR again.
Worth knowing. GPCRs are found only in eukaryotes, never in prokaryotes, and humans use a very large number of different ones. If a question mentions a prokaryote and a GPCR in the same sentence, something is wrong.
Receptor tyrosine kinases
Receptor tyrosine kinases (RTKs) are a class of transmembrane receptors responsible for many different signal transduction pathways and cellular responses.
An RTK is activated by a ligand binding at the external region of the membrane.
After binding, the intracellular portion becomes phosphorylated, using phosphate groups from ATP.
The activated RTK stimulates assembly of relay proteins, which carry the signal onwards.
One RTK can trigger multiple different signal transduction pathways simultaneously.
The action of insulin
Insulin triggers increased uptake of glucose in target cells such as fat storage cells, adipose cells, muscle cells and liver cells. It does this through an RTK.
The vesicles already exist inside the cell, loaded with transporter proteins. Insulin’s real job is telling them to fuse with the membrane.
🧩 Insulin, step by step
Insulin binds to the extracellular binding site of an RTK in the membrane of a target cell.
This triggers phosphorylation of tyrosine on the inner portion of the receptor.
That stimulates production of relay proteins.
The relay proteins cause vesicles containing glucose transporter proteins to fuse with the cell surface membrane.
More transporters means the cell is more permeable to glucose, so the rate of facilitated diffusion of glucose into the cell increases.
The three receptors side by side
Receptor
What binding does
Typical response
Ligand-gated ion channel
Shape change opens the channel
Ions flow in and membrane potential changes — very fast
GPCR
Conformational change activates a G-protein; GTP replaces GDP
Subunits act on enzymes and ion channels, often via second messengers
Receptor tyrosine kinase
Inner portion is phosphorylated using ATP
Relay proteins assemble; several pathways can run at once
Worked examples
WE 1
Explain how ACh changes membrane potential
Explain how acetylcholine causes a change in membrane potential at a cholinergic synapse. (4 marks)
Point 1: binding
ACh diffuses across the cleft and binds to ligand-gated sodium ion channels in the postsynaptic membrane.
Point 2: the shape change
Binding causes a shape change in the channel, which opens it.
Point 3: the ion movement
Positively charged Na+ ions diffuse down a gradient into the cytoplasm of the postsynaptic neurone.
Point 4: the effect
This reverses the charge across the postsynaptic membrane, initiating a new nerve impulse.
Bind, open, ions in, charge reversedadd that acetylcholinesterase breaks ACh down if the question asks why stimulation stops
WE 2
Describe G-protein activation
Describe how a G-protein is activated and later switched off. (4 marks)
Point 1: the trigger
A non-steroid ligand binds to the GPCR, causing a conformational change that activates the attached G-protein.
Point 2: the swapGTP replaces GDP on the G-protein.
Point 3: dissociation
The G-protein dissociates from the GPCR as a GTP-bound alpha subunit and a beta-gamma dimer, which interact with other membrane proteins and can release second messengers.
Point 4: switching off
The G-protein returns to its inactive state when GTP is hydrolysed to GDP, and it associates with the GPCR again.
GDP off, GTP on, hydrolysis back to offname both parts — “alpha subunit” and “beta-gamma dimer” are separate marking points
WE 3
Explain how insulin increases glucose uptake
Explain how insulin binding to a receptor tyrosine kinase increases glucose uptake by a liver cell. (4 marks)
Point 1: binding and phosphorylation
Insulin binds to the extracellular site of the RTK, triggering phosphorylation of tyrosine on the intracellular portion using phosphate from ATP.
Point 2: relay proteins
This stimulates the production of relay proteins that carry the signal onwards.
Point 3: the vesicles
Relay proteins cause vesicles containing glucose transporter proteins to fuse with the cell surface membrane.
Point 4: the result
Permeability to glucose increases, so the rate of facilitated diffusion of glucose into the cell rises.
More transporters in the membrane, so more glucose diffuses insay facilitated diffusion, not active transport — the glucose is not pumped
💡 Exam tips
Call the ACh channel a ligand-gated sodium ion channel and note that it is a specialised transmembrane receptor.
Use the phrase reverses the charge for the postsynaptic membrane.
Name acetylcholinesterase, and add that the products are recycled.
For GPCRs, remember GTP is active, GDP is inactive, and that they exist only in eukaryotes.
For RTKs, say the receptor becomes phosphorylated using phosphate groups from ATP.
For insulin, finish with facilitated diffusion and increased permeability.
⚠ Common mistakes
Saying ACh enters the postsynaptic neurone. It binds to the channel and stays outside.
Saying sodium ions are pumped in at the synapse. They diffuse down a gradient through an open channel.
Mixing up GTP and GDP. Triphosphate is the active one.
Saying the whole G-protein leaves as one piece. It splits into an alpha subunit and a beta-gamma dimer.
Saying insulin carries glucose into the cell. Insulin never enters; it adds transporters to the membrane.
Calling glucose uptake active transport. The transporters allow facilitated diffusion.
Up next: Epinephrine Receptors. We have seen a G-protein switch on. Next we follow what happens after it, through cyclic AMP and an enzyme cascade that turns one hormone molecule into a very large amount of glucose.
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