Chemical Signalling

what are the basic stages of a cell signalling pathway?

• stimulus or signal is received by a receptor

• a signal is converted to a signal that can be passed on → transduction

• the signal is transmitted to a target (effector)

• an appropriate response is made

what is a ligand?

a signalling molecule

what are some examples of ligands?

• proteins and amino acids

• nucleotides

• steroids

• amines

what are the stages of a cell signalling pathway involving ligands?

• secreted from the sending cell into the extracellular space

• transported to a target cell

• bind to surface receptors (that are specific to that ligand) on the target cell

• message carried by the ligand is relayed through a chain of chemical messengers inside the cell, triggering a response

what is quorum sensing?

how bacterial colonies monitor their size to assess when a threshold has been reached → bacteria can alter their gene expression

what is the mechanism for quorum sensing?

• ligands released by bacteria bind to receptors on the surface of other bacteria

• the more bacteria present the more ligands released

• when a threshold number of receptors are occupied, a change in gene expression is triggered

• a change in gene expression leads to a change in activity signalling a quorum has been met in the colony

what are the mutualistic associations between vibrio fischeri and bobtail squid?

• for squid → increased camouflage as bacteria emit light by bioluminescence making the squid less visible against the bright sky

• for bacteria → provided with amino acids and sugar from squid’s metabolic processes

how do vibrio fischeri enable the squid to produce light?

• colonise the light organ in the squid and release a ligand called an autoinducer

• the more bacteria, the more autoinducer

• autoinducer enters other bacterial cells and binds to the LuxR receptor in the cytoplasm

• when enough autoinducer-LuxR complexes have formed, a threshold is reached

• so there is transcription of DNA that leads to the synthesis of the enzyme luciferase

• luciferase catalyses an oxidation reaction that releases energy as bioluminescence

what are hormones?

chemical substances produced by a gland and carried by the blood that alter the activity of one or more target organs

which glands produce hormones?

endocrine glands

where are hormones transported?

in the blood

what cells do hormones affect?

only cells with target receptors → must be complementary shape to hormones for bonding to occur

what are neurotransmitters?

chemicals that transmit signals across the synaptic cleft from the presynaptic to the postsynaptic neurone

what happens in the process of neurotransmitters transmitting an action potential across the synapse?

• neurotransmitters diffuse across the synaptic cleft and bind with receptor molecules on the postsynaptic membrane

• this causes sodium ion channels on the postsynaptic membrane to open allowing sodium ions to diffuse into the postsynaptic cell

• if enough neurotransmitters bind with receptors on the postsynaptic membrane then a nerve impulse is generated

• the neurotransmitters are then broken down to prevent continued stimulation

what are cytokines?

proteins released by nearly every cell in the body, determine the activity of other cells

how do cytokines interact with cells?

by binding to receptors on the cell surface membrane, they cannot enter the cytoplasm

what does the binding of cytokines cause?

a cascade effect inside the cell affecting gene expression and cell activity

what do calcium ions do during a muscle contraction?

an influx of Ca²⁺ initiates a change in shape of specific proteins that allow contraction of fibres within muscle tissue

calcium ions pumped back out of the muscle fibres so the response is rapid and short-lived

what do calcium ions do at the synapse?

the arrival of a nerve impulse stimulates the movement of calcium ions into the presynaptic knob from the synaptic cleft which then triggers vesicles to release neurotransmitters into the synapse

calcium ions pumped back into synaptic cleft so response is rapid and short-lived

what are the three categories of hormones?

amines, peptides and steroids

what are the properties of amines and proteins?

hydrophilic so difficult to cross phospholipid bilayer so they bind to external membrane receptors

what are the properties of steroids?

hydrophobic so can cross cell membranes and bind to receptors inside cells

are neurotransmitters hydrophobic or philic?

hydrophilic → so bind to cell surface receptors

what is the comparison between hormones and neurotransmitters?

• neurotransmitters have a localised effect

  • short distance to diffuse from pre to postsynaptic membrane

• hormones have a more distant effect

  • travel larger distances in the blood

what are transmembrane proteins?

receptors located in the cell membrane with an external binding site and an internal region (extend across the width of the membrane)

what are the characteristics of transmembrane proteins?

• hydrophilic amino acid regions at either end of the protein in contact with the aqueous solution inside and outside the cell

• hydrophobic amino acid region within the membrane in contact with the hydrophobic tails of the phospholipids in the cell membrane

what is the cascade of events following the binding of a ligand called?

signal transduction pathway

what is the basic process of the signal transduction pathway?

• binding to the receptor

  • transmembrane → ligand binds to extracellular region of transmembrane receptor causing a change in shape to the internal region

  • intracellular → ligand binds to intracellular receptor forming a ligand-receptor complex

• signal transduction through multiple events

  • transmembrane → transmembrane proteins initiate a signal transduction pathway involving phosphorylation events and a second messenger

  • intracellular → ligand-receptor complexes are activated to follow a signal transduction pathway

what are some cellular responses to a signal transduction pathway?

• regulation of gene expression through control of transcription or translation

• change in metabolic activity

• regulation of enzyme activity

• cell death

• rearrangement of cell cytoplasm

• regulation of proteins eg channels in plasma membrane

what is membrane potential?

the charge across a nerve cell membrane

what is the mechanism by which acetylecholine changes membrane potential?

• arrival of an action potential at the presynaptic membrane stimulates the release of ACh into synaptic cleft

• ACh molecules diffuse across the synaptic cleft and temporarily bind to ligand-gated ion channels in the postsynaptic membrane → specialised transmembrane receptors

• this causes a shape change in the sodium ion channel which then opens allowing Na⁺ ions to diffuse down a gradient into the cytoplasm of the postsynaptic neurone

• the sodium ions reverse the charge across the postsynaptic membrane, initiating a new nerve impulse in the postsynaptic neurone

• ACh molecules are then broken down using acetylcholinesterase to prevent continued stimulation

• the products are then absorbed back into the presynaptic membrane, recycled and packaged into vesicles to be used when another action potential arrives

what is a g protein coupled receptor?

a transmembrane receptor protein responsible for the activation of a special intracellular protein called a G protein

what is GTP?

guanine triphosphate → active G proteins

what is GDP?

guanosine diphosphate → inactive G proteins

how are G proteins activated?

• a non-steroid ligand binds to the GPCR on the outside of a cell

• a conformational change occurs activating the attached G protein

• GTP replaces GDP on the G-protein, which then dissociates from the GPCR in two parts

  • GTP-bound alpha subunit

  • beta-gamma dimer

what are some targets of activated G proteins?

enzymes and ion channels

how do G-proteins return to their inactive state?

when GTP is hydrolysed to GDP, and they reassociate with the GPCR

what are receptor tyrosine kinases?

types of transmembrane receptors responsible for many signal transduction pathways and cellular responses

how are receptor tyrosine kinases activated?

• ligand binds to the external region of the cell membrane

• intracellular portion of the receptor becomes phosphorylated using phosphate groups from ATP

• activated receptor tyrosine kinase stimulates the assembly of relay proteins → responsible for onward signal transduction pathway

• one RTK can trigger mutiple signal transduction pathways simultaneously

what is insulin?

a hormone that triggers an increased uptake of glucose in target cells

how do receptor tyrosine kinases work with insulin?

• RTKs in cell membranes of target cells are activated when insulin binds

• triggers the phosphorylation of tyrosine which stimulates production of relay proteins

• these relay proteins then cause vesicles containing glucose transporter proteins in the cell cytoplasm to fuse to the cell surface membrane, adding more glucose transporter proteins to the membranes

• this increases the permeability of the cells to glucose and increases facilitated diffusion of glucose into the cell

what does epinephrine do?

increases blood glucose concentration in response to biological stress

how does epinephrine bring about a response?

binds to receptors on the outside of the cell and brings about an intracellular response using the second messenger model

what are second messengers?

molecules/ions in cells that relay signals received by cell surface receptors

how does the second messenger model work? (for epinephrine)

• epinephrine binds to specific receptors on the membrane of liver cells

• causes the enzyme adenyl cyclase to change shape and become activated

• active adenyl cyclase catalyses the conversion of ATP to the second messenger, cyclic AMP (cAMP)

• cAMP binds to protein kinase A enzymes activating them

• active protein kinase A enzymes activate phosphorylase kinase enzymes by adding phosphate groups to them

• active phosphorylase kinase enzymes activate glycogen phosphorylase enzymes

• active glycogen phosphorylase enzymes catalyse the breakdown of glycogen to glucose

what is the breakdown of glycogen to glucose called?

glycogenolysis

what is a transcription factor?

a protein that controls the transcription of genes by binding to a specific region of DNA

what is the oestradiol stimulation pathway?

1. Oestradiol diffuses through the cell surface membrane into the cytoplasm

2. Oestradiol diffuses through a nuclear pore into the nucleus

3. Within the nucleus oestradiol attaches to an ERalpha oestradiol receptor held within a protein complex, causing it to undergo a conformational change

4. the new shape of the receptor allows it to detach from the protein complex and diffuse towards the gene to be expressed

5. The ERalpha oestradiol receptor binds to a cofactor which enables it to bind to the promoter region of the gene, this stimulates RNA polymerase binding and gene transcription

what is oestradiol?

a steroid hormone responsible for the regulation of female sexual characteristics

where is oestradiol produced?

the ovaries, placenta and testes

what are the effects of oestradiol?

• gonadotropin releasing hormone is released from the hypothalamus

• this stimulates the release of LH and FSH from the pituitary gland

• these hormones are responsible for the menstrual cycle woth target cells in the uterus, breasts and bone marrow

• oestradiol can either inhibit or promote the release of gonadotropin-releasing hormone throughout the menstrual cycle resulting in either positive or negative feedback response

what is progesterone?

a steroid hormone responsible for the maintenance of the endometrial lining in preparation for implantation of an ovum

where is progesterone produced?

the corpus luteum and placenta

what are the effects of progesterone?

• enters the cytoplasm of a target cell and forms a ligand-receptor complex, leading to expression of a range of genes

• on example of a gene transcribed and translated is a growth factor which promotes cell proliferation required to replenish the endometrial cells of the uterus

what are the steps of negative feedback loops?

• receptor detects a stimulus

• coordination system transfers information between parts of the body

• effector carries out a response

what are the outcomes of a negative feedback loop?

if there is an increase in the factor the body responds to make the factor decrease and vice versa

example of positive feedback

the cervix dilating during labour

• the cervix stretches as the baby pushes against it

• stretch receptors are stimulated and send impulses to the brain

• the pituitary gland releases oxytocin which increases the intensity of uterine contractions

• pushes the baby further down the birth canal and stretches the uterus further

how does positive feedback work in blood clotting?

• platelets become activated upon injury

• release chemicals that activate more platelets which will release chemicals activating even more etc etc

• ensures the wound is closed quickly to preovent infection & blood loss

• body will revert to negative feedback once the clot has formed