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Cell and Evolutionary Biology – Spring Term weeks 1 – 7
Cell Structure and Function
Cell – Membrane bound unit filled with an aqueus solution of chemicals, it has the capacity to
maintain itself, it can create copies of itself by dividing by 2
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Cell functions
 Aerobic – Need Oxygen
 Anaerobic – Do not need Oxygen
 Photoautotrophic – Use light energy to synthesise food
 Chemoautotrophic – Use inorganic energy sources (Hydrogen Sulfide HS)
 Heterotrophic – Digest organic compounds for nutrition
All Cells – Similar basic chemistry
DNA, Transcription, RNA, Translation, Protein
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 Repels – larger uncharged polar molecules (AA’s, glucose, nucleotides) and ions (H+, Na+,
HCO3-, K+, Ca2+, Cl-, Mg2+)
 All cells bound by membranes – Prokaryotes – no internal, limited subcompartments instead
Eukaryotes – Each organelle surrounded by 1 or more biomembrane
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Bilayer Membrane Structure – Lipid Molecules + Phospholipid Molecules (hydrophilic head, 2
hydrophobic tails)
Electron micrograph shows 2 polar layers forming a membrane
Lipids – 3 classes in membranes – Phosphoglycerides, Sphingolipids, Steroids
All 3 are amphiphatic but vary in chemical structure, abundance and function
Phospholipids
 Hydrophilic Head – dissolves in water
 Hydrophobic tails – cannot bond with water
 Amphipathic – molecules have polar hydrophilic head and hydrophobic tail – subject to 2
conflicting forces
Phosphoglycerides – Most abundant lipid class in membranes
 Derivative of glycerol – 3 – phosphate
 Contains 2 esterified fatty acyl chains
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g
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(has no effect in SM layer)
Bilayer Curvature – PC – cylindrical – forms flat monolayers, PE – smaller head – conical shape –
forms natural curve in membrane
Micelle – water soluble spherical arrangement of phospholipids, forms spontaneously in aqueous
solution
Liposome – artificial spherical phospholipid bilayer structure, aqueous interior, forms in vitro, may
contain membrane proteins
Proteins in bilayer – some cross bilayer, others are on top or embedded in the bilayer
Membrane Proteins fluidity – Membrane proteins are free to move within membrane plane
E
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Human + mouse membrane protiens  mixed after hour
 Mixing is essential for membrane function – diffusion, distribution, fusion and division
 Maintained within limits – will not be too or too little fluid
 Determined by phospholipid composition (more closely packed tails = less fluid) and
temperature (increase temp – more movement = more fluid
Heat disorders non polar tails, causes membrane to turn from gel like to fluid like
Lipid Bilayer – Asymmetrical – 2 halves differ due to different proteins and phospholipids
Assymetry
 Generated in the cell
 Inside (cytosolic face) – exposed to cytosol
 Outside (non cytosolic face) – exposed to cell exterior/organelle interior (glycolipids only
occur in this part of the membrane
Membrane Proteins - Carry out membrane functions, make up 50% of mass of plasma membrane
Membrane Protein Functions
 Transport
 Enzyme Activity
 Signal transduction
 Cell – Cell recognition
 Intercelluar Joining
 Attachment to cytoskeleton and Extracellular Matrix (ECM)



Associate with lipid bilayer – integral proteins (transmembrane (crossing membrane) and
lipid linked) Peripheral proteins (protein linked)

Transmembrane Proteins – Hydrophobic AA’s or alpha helix, act as membrane transport proteins,
have aqueous pore
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Gradient
Osmosis – passive – with conc
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Gradient – uses carrier proteins
Active Transport – uses ATP, e
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pumping K+ and Na+ against conc
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Optical – light, lab work
Florescence – sample is light source, specimens can be made to fluoresce to study them (add GFP
green fluorescent protein), certain materials emit energy detectable as light when irradiated with
specific light wavelength
Live Cell imagaing – in cell analyser - stained cells visible while alive (method 1), in IncuCyte – system
provides continuous time lapse images of live cells – graphs can be drawn to show movement
Electron Microscope – achieves greater resolution than light microscope, wavelength of electron
shorter than wavelength of light = 2M x Magnification
Atomic Resolution Analytical Microscope – 50M x Magnification

Organelles – Eukaryotic cells have organelles, creating intracellular compartments (intra = inside,
inter = between)
 Held in place by cytoskeleton, move around on cytoskeletal tracks
 Occupy half of cell volume, increase membrane component of cell (ER membrane 20x
greater than plasma membrane)
Compartments and Main Functions
Cytosol – many metabolic pathways e
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protein synth
Nucleus – main genome, DNA/RNA synth
ER – Lipid and protein synth and distribution
Golgi – Modification, sorting, packaging of proteins and lipids
Lysosomes – Intracellular degradation
Chloroplasts – ATP synth and carbon fixation via photosynthesis
Mitochondria – ATP synth by oxidative phosphorylation
Peroxisomes – Oxidation of toxic molecules
Organelles
Information processing – Nucleus, Ribosomes
Energy processing – Mitochondria, chloroplasts (plastids)
Endomembrane System (pack, transport, distribute) – ER, Golgi, Lysosomes, Peroxisomes
Nucleus
 Most prominent organelle



Enclosed by nuclear envelope formed of 2 concentric membranes – inner = binding site for
chromosomes, outer = is continuous with ER
 Envelope perforated by nuclear pores (has approx
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Chromosome Structure – Chromosomes – long linear DNA structures, associated with proteins that
fold and pack DNA thread – collectively called chromatin
Eukaryotes have interphase chromosomes
DNA Packing – Basic Unit - Nucleosomes – “beads on a string” = core particles + linker DNA
Core particles – 8 histone proteins (2x(H2A, H2B, H3 and H4) and a + charged AA
Has 146 base pairs of DNA
Linker DNA – has 50 base pairs of DNA
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H1 Histone binds to DNA adjacent to core, nucleosomes packed to generate 30nm of fibre
3
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Mix of enzymes – e
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krebs cycle
 Mitochondrial genome on circular DNA molecule
 Ribosomes
Inner Mitochondrial Membrane
 Cristae – folds increase SA
 Very selectively permeable to transport proteins
 Site of electron transport chain in ATP synth
Outer Mitochondrial Membrane
 Has porins – large channel forming proteins
 Highly permeable
 Site of mitochondrial lipid synth
Intermembrane Space
 Similar composition to cytosol, contains kinases – enzymes that use ATP to phosphorylate
other molecules
Mitochondrial DNA (mt DNA)
 Separate to nuclear DNA
 Endosymbiotic Theory – mitochondria has the genome of bacteria, was engulfed by
eukaryotic cell
 Inherited from mother as sperm mitochondria normally destroyed, some genes for proteins
are found in mitochrondria, not nucleus
 More susceptible to damage by reactive Oxygen species from respiration than nuclear DNA,
despite mt DNA protein packaging
Mt DNA and diseases – Damage to mt DNA is thought to contribute to Parkinsons, Disonia, MND,
Atassia, corea
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For pyrimidine metabolism
and mitochondrial shuttle
 Matrix – for citric acid cycle – citrate synthase
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(10-8M or less)
 Receptors must have a high affinity to bind to specific ligand
Panacrine – signals released into extracellular space
 Act as local mediators – act on neighbours only
 Act only on proper target cells – must not diffuse too far – this is controlled by rapid uptake
by extracellular enzymes or immobilisation by ECM
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Achieved in synaptic cleft – neurotransmitter releatively low affinity for ligand,
dissociate rapidly from receptor to terminate response
 Neurotransmitter action limited by uptake and enzymatic mechanisms
 Synaptic more precise in time and space than endocrine
Contact Dependant – requires cells to be in direct contact via membrane bound signalling molecules
+ complementary receptors on target cells
 Signalling important in development and immune response

Autocrine – group of identical cells produces high conc
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Nicotoionic ACh receptors in skeletal muscle  contraction
Muscarinic ACh receptors in heart muscle  decreased contraction + force
 Intracellular signalling machinery present in cell – it intergrates and interprets signals the cell
receives
Muscarinic ACh receptors in heart muscle and salivary gland
Extracellular Signals – Response Speed – depends on delivery mechanism and nature of response
 Ionic Changes – milliseconds, 2nd messenger synthesis – seconds  mins, gene expression
and new protein synth – hours
 E
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rapid phosphorylation by protein kinases – seconds
 E
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cell movement/secretion/metabolism changes – seconds – mins
 E
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cell growth/division – needs gene expression + new protein synth – hours
Gap junctions – allow neighbouring cells to share and co-ordinate signals
 Direct channel between opposed plasma membranes – connects cytoplasm, small
intracellular signalling molecules can be exchanged e
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AMP, Ca2+, also 2nd messengers
 During development cells make/break gap junctions in patterns to co-ordinate cell
behaviour e
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gap junction protein Connexin 43 – without which mice have severe heart
defects
Rapid turnover + conc
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(vice versa –slow turnover – slow conc
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g intracellular signal Cyclic AMP activates protein kinase enzyme PKA, PKA activation
requires 4 cAMP to bind to PKA
Receptors – signal transduction – extracellular signal binds – IN
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not absoloute conc
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Unstimulated – receptor + G protein both in active, either separate or in a preformed
complex
2
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Alpha subunit of G protein changes – allowing it to exchange GDP for GTP
4
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Activating beta gamma activates the K+ channel
6
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Inactivation of G protein – switching off of G protein alpha subunit by hydrolysis of its bound GTP
1
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This inactivates alpha, alpha dissociates from target protein, ressociates with beta gamma
complex, reforming inactive G protein
The binding to the target protein/membrane bound regulator of G protein signalling stimulates
GTPase activity of alpha subunit - Therefore Stimulation speeds up activation

Extracellular Signal molecule  binds to cell surface receptor  sends intracellular signalling
molecules (2nd messenger)
2nd Messenger – small intracellular signalling molecules
 Generated in response to receptor activation
 Diffuse away from source rapidly
 Transmit signal to other cell parts
 E
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cAMP, cGMP, Calcium
Cyclic AMP – cAMP – mediates several responses – adrenaline in muscle/heart, glucagon in liver
 1st messenger receptor G protein Enzyme + ATP  cAMP (2nd messenger)  protein
kinase A
 Activates multiple intracellular signalling pathways – Most via PKA
 Slow effects – activating gene transcription via increase in cAMP conc
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kept low
 Actively pumps Ca2+ out of cell
 Pump Ca2+ into ER and mitochondria and other molecules that bind Ca2+ tightly
 Ca2+ mediates responses using calmodulin
 Ca2+ + Calmodulin = activated enzyme, no calmodulin = inactive enzyme
Enzyme Linked Receptor – 6 Families
 Receptor tyrosine kinases – phosphorylate specific tyrosines
 Tyrosine–Kinase–associated receptors – asscociate with intracellular proteins with tyrosine
kinase activity
 Receptor-Like tyrosine phosphases – remove phosphate groups from tyrosines, “receptor
like” – ligand not identified
 Receptor serine/theonine kinases – phosphorylate specific serines/theronines
 Receptor guanylyl cyclases – catalyse cyclic GMP production
 Histadine- kinase-associated receptors – activates phosphorylation of histadine and
immediately transfers to an intracellular signalling protein
Different families have own subfamilies – have different morphologies – need to be recognised by
different ligands
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Parkinsons – Lewy Bodies – clumps of protein in brains of people with PD
Endoplasmic Reticulum Stress – caused by calcium overload/misfolded proteins  cell death
Excitotoxcity – over excitation of neurones – involves glutamate/ Ca2+/ Free radicals(oxidative stress)
Glutamate paradox – L – glutamate – major excitatory neurotransmitter in CNS
 Involved in complex functions – learning, memory, synaptic plasticity
 Involved in survival signalling
 =( potentially neurotoxic – causes neuronal damage  neuropathology diseases
Neuropathology diseases
 Stroke (cerebral ischaemia)
 Foetal ischaemia
 AD, PD, HD, motor neurone disease
 Damage during epilepsy, alchohol withdrawal
 Damage post head trauma
 Age related cognitive decline
Glutamate – is a ligand – activates glutamate receptors
2 receptors types – Iontropic ligand gated ion channels, Metabotropic  2nd Messenger system
Excitotoxicity – production of RNS, ROS, free radicals
ROS – reactive oxygen species, RNS – Reactive Nitrogen species
Ca2+ also produces reactive Oxygen species – can move through receptors to cause damage
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Eukaryotes – DNA inside nucleus
Cell cycle – ordered set of events, culminating in cell growth and division into 2 daughter cells
Mitosis – mitosis is nuclear division + cytokinesis, producing 2 identical daughter cells – prophase,
promataphase, metaphase, anaphase, telophase
Meiosis – form of cell division in sexually reproducing organisms, 2 consecutive nuclear divisions
occur without chromosomal loss, replication between  4 haploid gametes – all contain 1 of every
pair of homologous chromosome
Eukaryotic gene regulation – regulation of transcription, splicing and processing, transport,
degredation of mRNA, translational regulation, protein modification
Aneuploidy – abnormal number of chromosomes
Cell cycle – key regualtors discovered in 2001 – Paul Nurse, Leland hartwell, timothy hunt
Interphase and mitosis, interphase – G1 (gap phase 1) S (synthesis) and G2 (gap phase 2)
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GO – typically long lasting state – cell cycle progression postponed till signal received
Regulation of cell cycle transitions – controlled by protein phosphorylation by CDK’s and degredation
by proteasomes of proteins and marked by ubiquitination
Irreversibility of protein degredation drives cell cycle in 1 direction, phosph/dephosphorylation
enables rapid changes
Diffusable factors – evidence for presence of a diffusible component in mitotic cells that can induce
mitosis in G1 cells
Mitosis control by cyclins + MPF activity – Maturation promoting factor – MPF – protein kinase
(requires mitotic cyclin) – stimulates mitosis, “mitosis promoting factor”
Increases + decreases in MPF activity during cell cycle in early embryo reflects cyclic synth +
degradation of mitotic cyclins
Anaphase – promoting complex cyclosome (APC/C) ubiquitin ligase – recognises destruction box
sequence in mitotic cyclins – marks for degradation in late anaphase + this terminating mitosis
Deactivation of APC/C (by G1- cyclin/CDK) in G1 permits mitotic (+S phase) cyclins to accumulate 
allowing continuation of cell cycle
Studies on MPF activity conducted on Xenopus (African clawed toad)
Studies on mitotic cyclin destruction conducted on sea urchins
Temperature sensitive mutation – mutations that give rise to mutant proteins that exhibit increased
or decreased sensititivity to temperature
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