IB DP Biology: Chemical signalling: ligands, receptors and signal transduction (HL) (DP Biology)

This guide covers topic C2.1, Chemical signalling, from the IB Diploma Programme Biology guide, first assessment 2025, statements C2.1.1 to C2.1.14. The guide gives this topic no standard level content, so everything here is HL only (additional higher level). You can see it all on the IB DP Biology hub and tick it off on the printable checklist. For condensed recall use the revision notes, and test yourself with the practice questions. Try the free 10-minute diagnostics to see where you stand.

What you must be able to do

Statement	Focus	Tier
C2.1.1	Receptors are proteins with binding sites for a specific ligand	HL only
C2.1.2	Quorum sensing in bacteria; Vibrio fischeri bioluminescence	HL only
C2.1.3	Four functional categories of animal signal compared	HL only
C2.1.4	Why signals come in many chemical forms	HL only
C2.1.5	Local versus distant effects	HL only
C2.1.6	Transmembrane versus intracellular receptors	HL only
C2.1.7	Receptors start signal transduction pathways	HL only
C2.1.8	Acetylcholine receptor and membrane potential	HL only
C2.1.9	G protein-coupled receptors	HL only
C2.1.10	Epinephrine (adrenaline) and cyclic AMP	HL only
C2.1.11	Tyrosine kinase receptors; insulin	HL only
C2.1.12	Intracellular receptors and gene expression	HL only
C2.1.13	Oestradiol and progesterone on target cells	HL only
C2.1.14	Positive and negative feedback	HL only

Ligands and receptors (C2.1.1)

A signalling chemical is called a ligand. A receptor is a protein with a binding site whose shape and charge distribution fit one ligand, or a small family of similar ligands. Binding is reversible and uses weak bonds. It changes the shape of the receptor, and that change is the start of the response.

Specificity explains why a hormone in the blood affects some cells and not others. Every cell is exposed, but only target cells carry the matching receptor. Cells with different receptors respond to the same ligand differently, because the pathway behind the receptor differs.

Quorum sensing (C2.1.2)

Bacteria signal to one another by releasing small ligands called autoinducers. Each cell releases a little. At low population density the ligand diffuses away and its concentration stays low. As the population grows, the concentration rises. When it passes a threshold, enough ligand binds to receptors in the cells to switch on particular genes in the whole population at about the same time. This is quorum sensing: the population detects its own density.

Vibrio fischeri is a marine bacterium. In open seawater it is sparse and makes no light. In the light organ of a host such as a squid it reaches a very high density, and the genes for bioluminescence switch on. Light from one cell would be pointless, so a density-triggered response saves energy.

Worked example. A culture of V. fischeri was sampled at five densities (data supplied).

Density (million cells per cm³)	0.01	0.1	10	100	1000
Light output (arbitrary units)	0.02	0.2	80	12 000	250 000

Light per million cells is 2 at 0.01 and 0.1, then 8 at 10, 120 at 100 and 250 at 1000. Density rose 100 000-fold from 0.01 to 1000 but light rose 12 500 000-fold. Light per cell rose 125-fold from 0.1 to 1000, so each cell is producing more light at high density. That fits an autoinducer that accumulates and switches on bioluminescence genes above a threshold, between 0.1 and 10 million cells per cm³ here.

Categories of signalling chemical (C2.1.3 to C2.1.5)

Category	Made by	Travels	Typical effect
Hormone	Endocrine gland cells	In the blood, to distant targets	Slow, often long-lasting
Neurotransmitter	Neurons	Across a synaptic gap, about 20 nm	Fast, brief, very local
Cytokine	Cells such as immune cells	Mostly short distances between nearby cells	Regulate immune and inflammatory responses
Calcium ions	Released from stores or let in through channels	Within a cell	Trigger responses such as exocytosis and muscle contraction

Hormones can act far from their source because the blood system distributes them. They are diluted, so they work at low concentration and are removed by metabolism or excretion. A neurotransmitter is released into a gap so narrow that diffusion is quick and the concentration at the receptors is high. It is then removed, for example by enzyme breakdown or reuptake, so the signal stops within milliseconds.

Chemical diversity. Hormones include amines (epinephrine), proteins (insulin) and steroids (oestradiol, progesterone, testosterone). Neurotransmitters include amino acids (glutamate), peptides, amines (dopamine) and the gas nitric oxide. The official wording gives this gas as nitrous oxide, but the neurotransmitter gas is nitric oxide, NO.

Reasons for such variety include: different molecules suit different jobs, so lipid-soluble steroids pass into cells and are carried bound to proteins, while water-soluble proteins and amines dissolve freely in blood; a large number of distinct shapes lets many ligands each have a unique receptor, which reduces cross-talk; and different molecular sizes and stabilities give different lifetimes.

Where receptors sit (C2.1.6)

Feature	Transmembrane receptor	Intracellular receptor
Position	Spans the plasma membrane	In cytoplasm or nucleus
Ligand	Hydrophilic, or too large to enter	Hydrophobic, passes through the membrane
Amino acids	Hydrophobic in the stretch in the bilayer; hydrophilic in the parts in water outside and inside	Mostly hydrophilic outside, because the protein is dissolved in the cytoplasm or nucleoplasm
Examples	Acetylcholine receptor, insulin receptor	Oestradiol and progesterone receptors

The hydrophobic amino acids of the membrane-spanning part interact with the fatty acid tails of the phospholipids and hold the receptor in the bilayer.

Signal transduction (C2.1.7)

Signal transduction is the sequence of responses inside a cell that follows ligand binding. The ligand does not need to enter the cell. Instead the receptor changes shape, and this activates the next component, often an enzyme. Many steps allow amplification, because one active enzyme makes many product molecules (for example, one active adenylyl cyclase makes many cAMP), and they give several points of control. A pathway also needs an off switch, otherwise the cell would respond for ever.

The acetylcholine receptor (C2.1.8)

The acetylcholine receptor is a transmembrane protein that is also an ion channel. When acetylcholine binds, the channel opens and positively charged ions, mainly sodium ions, diffuse into the cell down their gradient. The inside of the membrane becomes less negative, a depolarisation. If this reaches a threshold, other changes follow, such as opening of voltage-gated channels and an action potential.

Worked example. A neuron has a resting potential of −70 mV. After acetylcholine arrives it is −52 mV. The threshold is −50 mV (data supplied).

• Change: −52 − (−70) = +18 mV, a depolarisation.
• The potential is 2 mV short of threshold, so no action potential is triggered.
• More receptors opening, from more acetylcholine, would bring the potential to −50 mV or above and trigger one.

G protein-coupled receptors and epinephrine (C2.1.9 and C2.1.10)

Humans have a large number of G protein-coupled receptors. Each is a single protein crossing the membrane several times. On the inner face a G protein is attached. The sequence is:

1. The ligand binds on the outside and the receptor changes shape.
2. The G protein exchanges GDP for GTP and becomes active.
3. The active G protein activates an enzyme in the membrane.
4. The enzyme makes a second messenger, which spreads through the cytoplasm.
5. GTP is hydrolysed, the G protein switches off, and the second messenger is broken down.

Epinephrine (also called adrenaline) is a hormone from the adrenal gland. Both names come from words for “at/above the kidney”. In a liver cell, epinephrine binds its receptor, the G protein activates adenylyl cyclase, which converts ATP to cyclic AMP (cAMP). cAMP activates protein kinase A, starting a cascade that activates enzymes breaking glycogen down, so glucose is released into the blood. An enzyme, phosphodiesterase, breaks cAMP down and ends the signal.

Worked example. Liver cells were exposed to epinephrine at 0 s and it was washed away at 60 s. cAMP (arbitrary units) was 4 at 0 s, 60 at 15 s, 88 at 60 s, 31 at 120 s and 6 at 300 s (data supplied).

• At 60 s cAMP is 88/4 = 22 times the starting level.
• Between 60 s and 120 s it fell by 57 units, which is 64.8% (57/88 × 100).
• It falls once epinephrine is removed because the receptor stops activating G proteins and phosphodiesterase keeps destroying cAMP.

Tyrosine kinase receptors and insulin (C2.1.11)

Insulin is a protein hormone that cannot cross the membrane. It binds to its receptor in the plasma membrane, which has tyrosine kinase activity. A kinase transfers a phosphate group from ATP to a protein. Binding causes phosphorylation of tyrosine inside the cell, which starts a sequence of reactions. It ends with vesicles carrying glucose transporters moving to the plasma membrane and fusing with it. More transporters means faster uptake of glucose by facilitated diffusion.

Worked example. Glucose uptake by muscle cells (µmol per g per hour, data supplied): no insulin 2.4; insulin 9.6; insulin plus a tyrosine kinase inhibitor 3.0.

• Insulin raises uptake by 9.6 − 2.4 = 7.2, a 300% increase (fourfold).
• The inhibitor removes 9.6 − 3.0 = 6.6 of that rise, which is 6.6/7.2 × 100 = 91.7%.
• This supports the idea that tyrosine kinase activity is needed for the insulin effect.

Intracellular receptors (C2.1.12 and C2.1.13)

Steroid hormones are lipid-soluble and pass through the plasma membrane. Inside, the ligand binds to its receptor. Once activated, the receptor attaches to particular DNA sequences and promotes transcription of chosen genes. New mRNA and then new protein appear, so the response is slower than a membrane pathway but longer lasting.

• Oestradiol acts on the hypothalamic cells that release gonadotropin-releasing hormone (GnRH), changing GnRH secretion. In the usual account, modest oestradiol levels reduce GnRH release (negative feedback), while the high, sustained levels late in the follicular phase of the menstrual cycle increase it (positive feedback).
• Progesterone acts on cells of the endometrium, supporting the lining so that it is ready for an embryo to implant.

Feedback (C2.1.14)

Negative feedback reverses a change, which stabilises a variable. Example: a high blood glucose concentration stimulates insulin release, glucose uptake lowers glucose, and insulin release falls. Positive feedback amplifies a change. Example: during labour, stretching of the cervix triggers oxytocin release, oxytocin strengthens contractions, and stronger contractions cause more stretching.

Common errors

• Writing that the ligand “enters” a transmembrane receptor. It binds outside and the receptor changes shape.
• Saying a hormone only reaches its target. It reaches all cells; only target cells respond.
• Calling cAMP the first messenger. The hormone is the first messenger and cAMP the second.
• Mixing up the effect of GTP: the G protein is active with GTP bound.
• Describing insulin as entering cells.

Official syllabus

IB Diploma Programme Biology guide, first assessment 2025, published by the International Baccalaureate Organization. Topic C2.1, Chemical signalling (additional higher level).