Biology - chemical signalling

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cell signalling

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1

cell signalling

the process by which messages are cent to cells, allows multicellular organisms to control and coordinate their bodies and respond to the environment.

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2

basic stages of cell signalling

  • stimulus received by receptor

  • signal converted to signal that can be passed on (transduction)

  • signal transmitted to target (effector)

  • appropriate response is made

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3

Ligands

  • signalling molecules such as proteins, amino acids, nucleotides, steroids, and amines.

  • they are secreted from a cell into extracellular area

  • then transported to target cell

  • message carried is relayed through a chain of chemical messengers inside the cell

  • response is triggered

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4

quorum sensing in bacteria

  • bacteria communicate with ligands

  • can respond to changes in population size by a series of gene expressions

  • quorum sensing is when a bacterial colony will monitor its size till a threshold is reached.

  • ligand released by bacteria binds to receptors of other bacteria

  • more bacteria means more ligands

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

  • leading to change in activity which signals quorum has been met

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5

vibrio fischeri relationship

  • species of bacterium found in marine environments

  • form mutualistic associations with some species of squid

  • benefit to squid: increased camouflage due to bacteria bioluminescence

  • benefit to bacterial colony: transmission of amino acids and sugar

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process of bioluminescence

  • bacteria colonise structure inside the squid called light organ and release a ligand called autoinducer into extracellular environment

  • the more bacteria the more autoinducer released

  • autoinducers enter other bacterial cells and bind to LuxR in the cytoplasm

  • when enough autoinducer-LuxR complexes have formed, a threshold is reached, so transcription of DNA that leads to synthesis of enzyme luciferase

  • which catalyses the oxidation reaction which releases energy in bioluminescence

  • only occurs when colony is large enough to switch on synthesis of luciferase

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7

hormones

  • chemical substance which alters the activity of one or more target organs. ie chemicals which transmit information from one organ to another.

  • endocrine glands produce and secrete them into capillaries in the gland tissue (collectively these glands are called the endocrine system)

  • they are transported in the blood to target cells

  • only affect cells with target receptors which have to be complementary

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examples of hormones

insulin, glycogen, thyronine, testosterone

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9

neurotransmitters

  • chemicals that transmit signals across the synaptic cleft (pre-synaptic to post-synaptic neurones)

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

  • causes associated sodium ions to open

  • if enough neurotransmitters bind to receptor, then a nerve impulse is generated across post-synaptic neurone

  • neurotransmitters are then broken down to prevent continued stimulation

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10

examples of neurotransmitters

  • Acetylcholine

  • Norepinephrine

  • Dopamine

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11

cytokines

  • proteins released by nearly all cells in the body

  • several tyypes, each one plays a role in determining the activity of another cell

  • cannot enter cytopplasm so bind to membrane

  • leads to cascade ofd events which impact gene expression

  • involved in: immune response, cell growth, proliferation

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12

calcium ion

  • during muscle contraction, influx of Ca2+ changes shape of specific proteins

  • response is rapid and short issued

  • can act as second messengers in part of cascade of events

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13

categories of hormones

amines, peptides, steroids

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14

categories of neurotransmitters

amines, gases, amino acids, peptides

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15

transmembrane receptor proteins

  • located in cell membrane, have external binding site and internal region

  • characterised by: either hydrophobic amino acid in contact with aqueous solution inside and outside the cell

  • or hydrophobic amino acid in contact with hydrophobic tails inside membrane

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16

intracellular receptors

non polar, hydrophobic, ligands like steroids can diffuse through phospholipid bilayer and bind to receptors in the cytoplasm

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basic process of initiation of signal transduction pathways

  1. binding with receptor. (transmembrane: change of internal region, intracellular: ligand-receptor complex formed)

  2. signal transduction (transmembrane: phosphorylation, use of second messenger, intracellular: complex is activated)

  3. cellular response

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18

acetylcholine

ACh is a key neurotransmitter, synapses using ACh are known as cholinergic synapses. ACh can bring about a change in membrane potential (voltage) aka reversing charge in cell membrane

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19

mechanism behind reversing charge

  1. arrival of nerve impulse/ action potential at presynaptic membrane stimulates release of ACh

  2. It diffuses across synaptic cleft, temporarily binding to ligand-gated sodium ion channels

  3. causes shape change so they open allowng sodium ions to diffuse down a gradient into cytoplasm

  4. sodium ions reverse the charge across post synaptic membrane

  5. ACh molecules are then broken down using enzyme acetylcholinesterase to prevent continued stimulation

  6. products are absorbed back into presynaptic membrane, recycles, and packed into vesicles to use when another action potential arrives.

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20

g-protein-coupled-receptor

transmembrane receptor responsible for the activation of g-proteins which bind to either GTP (Active) or GDP (inactive) and act as a switch

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21

signal transduction using g-proteins

  • non-steroid ligand binds to GPCR in the outside of the cell, conformational change occurs which activates the attached g-protein

  • GTP replaces GDP on the G-protein which then dissociates from GPCR in 2 parts

  • parts: a GTP-bound alpha subunit anf a beta-gamma dimer

  • those sub units can interact with other membrane proteins and cause the release of second messengers

  • G-proteins return to their inactive state when GTP is hydrolysed to GDP and they associate again with GPCR

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22

RTK

  • receptor tyrosine kinase are a class of transmembrane receptor responsible for many cellular responses

  • activated by a ligand on external region of cell membrane

  • intracellular portion becomes phosphorylated using ATP

  • activated RTK then stimulates assembly of relay proteins responsible for onward transduction pathways

  • one RTK can trigger multiple STP simultaneously

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23

Action of insulin

  • insulin is a hormone that triggers increased uptake of glucose in target cells

  • .RTK of those cells are activated when insulin binds to extracellular site

  • triggers phosphorylation of tyrosine stimulating production of relay proteins

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

  • which increases permeability of cells to glucose

  • facilitated diffusion of glucose increases

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24

epinephrine receptors

  • epinephrine/adrenaline act to increase blood glucose concentration in response to biological stress

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

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second messenger

molecules/ions that relay signals received by cell surface receptors

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the second messenger model

  • epinephrine binds to specific receptors of liver cells

  • enzyme adenylyl cyclase changes shape and becomes activate

  • this activated enzyme catalyses the conversion of ATP to the second messenger cyclic AMP (cAMP)

  • cAMP binds to the protein kinase A enzymes, activating them

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

  • active phosphorylase activate glycogen phosphorylase enzymes

  • which catalyse the breakdown of glycogen to glucose in a process known as glycogenolysis

  • results in release of glucose

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27

transcription factor

a protein that controls the transcription of genes by binding to a specific region of DNA, if a gene is transcribed and translated then it is expressed

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steroid hormones

small, soluble, hydrophobic, lipid-bases, hormones that can diffuse through cell membranes and through nuclear pores. once inside they can bind to intracellular receptors

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29

oestradiol

controls female fertility cycle and stimulates sperm production.

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30

how oestroa works

  1. oestradiol diffuses through cell surface membrane into cytoplasm

  2. into nucleus through nuclear pores

  3. attaches to ERa oestradiol receptor held within a protein complex and causes the receptor to undergo conformational change

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

  5. ERa binds to a cofactor which enables it to bind to the promoter region of the gene and thereby stimluates RNA polymerase binding and gene transcription

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31

effects of oestradiol

  • responsible for regulation of female sexual characteristics

  • produced in ovaries, placenta, and testes

  • gonadotropin releasing hormone is first released from hypothalamus

  • stimulating release of luterising hormone and follicle stimulating hormone from pituitary gland. these hormones together are responsible for control of the menstrual cycle.

  • oestradiol can either inhibit or promote the release of gonadotropin releasing hormone, creating either positive or negative feedback

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32

progesterone

  • maintenance of endometrial lining

  • prevents further ovulation during pregnancy

  • produced by corpus luteum and placenta

  • progesterone enters cytoplasm of target cella and forms ligand-receptor complex creating the expression of a range of genes

  • eg. growth factor which promotes cell proliferation

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33

negative feedback

  • used to maintain a homeostatic balance

  • a receptor detects a stimulus. for example, a change in temperature

  • coordination system (nervous or hormonal) transfers information

  • effector (muscle or gland) carries out a response to reverse the change and bring back to normal limits

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34

positive feedback

when original stimulus produces a response that causes factor to deviate even more. Like blood clotting, or cervix expanding during birth. Useful to quickly activate a process.

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35

blood clotting

platelets become activated and release chemicals which activate more platelets etc. Ensures wound is quickly closed up and once blood clot has formed reverts to negative feedback.

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