C2.1 Chemical signalling [HL only]

Receptors are proteins that detect a particular chemical or physical signal and convert it into a cellular response.

Binding changes receptor conformation or channel state. Specificity comes from shape, charge and interactions, but the same receptor can trigger different outcomes in different cells because downstream machinery differs.

Explain receptor action:

• signal binds
• receptor changes state
• intracellular pathway activates
• cell response follows

Insulin binding to its receptor can activate signalling that increases glucose transporter insertion in a muscle-cell membrane.

A receptor detects a signal; it does not necessarily produce the final response by itself.

Quorum sensing lets bacteria estimate local population density by releasing and detecting signal molecules.

As cells accumulate, signal concentration rises. Once a threshold is reached, receptors activate coordinated gene expression such as bioluminescence, virulence or biofilm formation.

Trace the density signal:

• cells release an autoinducer
• concentration increases locally
• receptors detect a threshold
• many cells change gene expression

A bacterial colony may produce a biofilm only after enough cells release signal molecules to cross the response threshold.

Quorum sensing is coordination among cells, not direct communication through a nervous system.

Animal chemical signals differ in source, distance, speed and target-cell effect. Hormones are released by endocrine cells into blood and act at distant targets, usually more slowly. Neurotransmitters are released by neurons across synapses and act rapidly on nearby target cells. Cytokines are released by immune and other cells and coordinate local or systemic responses. Ca²⁺ ions act as short-lived intracellular signals that regulate target proteins.

• Hormone: endocrine source; bloodstream; distant target; relatively slow and longer-lasting.
• Neurotransmitter: neuron; synaptic cleft; adjacent target; rapid response.
• Cytokine: immune or other cell; local or body-fluid signalling; coordinates immune responses.
• Ca²⁺: intracellular messenger; changes protein activity inside the responding cell.
• Hormones can be protein/peptide, steroid or amine; neurotransmitters include acetylcholine, amino acids, peptides, amines and nitric oxide.

A localized signal acts near its source, whereas an endocrine signal travels through circulation to distant target cells.

Paracrine and synaptic signals reach nearby cells with short delays and limited dilution. Endocrine hormones can reach the whole body but only cells with the correct receptor respond.

Locate the signal’s range:

• autocrine: same cell
• paracrine: nearby cells
• synaptic: across a synapse
• endocrine: distant through blood

A neurotransmitter acts across a tiny synaptic gap, while thyroxine circulates and affects distant tissues with thyroid-hormone receptors.

Circulation makes a signal widespread, not automatically effective in every tissue.

The chemistry of a ligand determines whether it can cross the phospholipid bilayer. Hydrophilic ligands, such as peptide hormones and many neurotransmitters, cannot cross the non-polar membrane core, so they bind receptors on the cell surface and activate intracellular relay pathways. Lipid-soluble steroid and thyroid hormones cross the membrane and bind intracellular receptors in the cytoplasm or nucleus. The hormone–receptor complex can regulate transcription by acting on DNA.

• Hydrophilic ligand → cell-surface receptor → intracellular second messengers or kinase pathway.
• Lipid-soluble steroid/thyroid hormone → cytoplasmic or nuclear receptor → altered gene transcription.
• Receptor location matches ligand solubility, not simply the name of the hormone.

Signal transduction is the chain of molecular events linking receptor activation to a change in cell behaviour.

The chain may include conformational changes, G proteins, kinases, second messengers, transcription factors and feedback. Amplification allows a few signal molecules to influence many targets.

Map a pathway:

• receptor state changes
• relay or second messenger activates
• target proteins or genes change
• response is terminated

One activated receptor can stimulate many downstream enzymes, amplifying a small external signal into a measurable metabolic response.

A pathway is not complete until the signal is switched off or degraded; otherwise the cell cannot respond accurately.

Neurotransmitters bind receptors on a postsynaptic membrane and change ion permeability, altering membrane potential.

Ligand-gated channels open directly, while metabotropic receptors act through slower intracellular pathways. Excitatory currents depolarize toward threshold; inhibitory currents make firing less likely.

Interpret a postsynaptic effect by checking:

• ion channel or receptor type
• ion movement
• voltage change
• distance from action-potential threshold

Opening sodium channels can depolarize a neuron, whereas opening chloride channels may inhibit it by stabilizing or lowering membrane potential.

The same neurotransmitter can excite or inhibit different cells if their receptor subtypes differ.

A G protein-coupled receptor (GPCR) changes shape when a ligand binds and activates a membrane-associated G protein.

The activated G protein can regulate an enzyme or ion channel, generating second messengers such as cAMP. GTP hydrolysis and receptor desensitization terminate the signal.

Trace a GPCR pathway:

• ligand binds receptor
• receptor activates G protein
• effector changes second messenger or channel
• response is terminated

A GPCR can activate adenylyl cyclase, raise cAMP and activate protein kinase A in response to a hormone.

GPCR signalling is a relay; the receptor does not directly enter the nucleus or make ATP.

Adrenaline binds a GPCR and activates a cAMP pathway that rapidly promotes glycogen breakdown in target cells.

The receptor activates a stimulatory G protein, adenylyl cyclase makes cAMP, and a kinase cascade activates glycogen phosphorylase. Phosphodiesterase and receptor reset limit the response.

Follow the sequence:

• adrenaline binds receptor
• G protein activates adenylyl cyclase
• cAMP activates kinase
• glycogen becomes glucose units

One adrenaline molecule can trigger many cAMP molecules and therefore amplify glycogen breakdown during exercise.

Adrenaline does not directly split glycogen at the receptor; the kinase cascade mediates the response.

Tyrosine kinase receptors dimerize or rearrange after ligand binding and phosphorylate tyrosine residues that recruit signalling proteins.

Phosphorylated docking sites assemble a pathway controlling growth, survival or metabolism. The signal is terminated by phosphatases, receptor internalization or ligand removal.

Identify the core events:

• ligand-induced receptor pairing
• tyrosine phosphorylation
• docking of relay proteins
• downstream kinase cascade

A growth factor can activate a receptor tyrosine kinase and a Ras–MAP kinase pathway that changes gene expression and cell division.

More phosphorylation does not always mean more growth; pathway inhibitors and feedback constrain the signal.

Oestradiol and progesterone are steroid hormones that enter target cells and regulate gene expression through intracellular receptors.

Their effects depend on receptor distribution and cycle stage. Oestradiol can promote proliferative changes and feedback signals, while progesterone supports a secretory uterine state and modifies responses to oestradiol.

Interpret a hormone effect by checking:

• hormone concentration and timing
• receptor-containing tissue
• gene-expression response
• feedback to the reproductive axis

After ovulation, progesterone can reduce further follicle stimulation while preparing the uterine lining for possible implantation.

A steroid hormone has effects only where its receptor and downstream genes are present.

Feedback occurs when a response alters the signal pathway, either reducing further activation or amplifying it under defined conditions.

Negative feedback restores a variable toward a set range; positive feedback reinforces a change until a limiting event stops it. Receptors, hormones and downstream products can all participate.

Classify the loop:

• response opposes the original change: negative
• response reinforces it: positive
• identify the measured variable
• specify the stopping condition

Rising thyroid hormone suppresses hypothalamic and pituitary stimulation, whereas oxytocin-driven contractions can intensify until birth.

Calling any delayed response feedback is incomplete; the direction of the loop must be identified.