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LIPID DYNAMICS IN MEMBRANES
Diffusion occurs within membranes

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Lateral diffusion of lipids
o Very fast; D=1μm2
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e
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Mobility increases towards the bilayer centre
Tm depends upon
o Length of chain
o Degree of unsaturation
• Certain membrane transport processes and enzyme activities cease when the bilayer
viscosity is increased beyond a threshold level
• A synthetic bilayer made from a single type of phospholipid:
o Changes from a liquid state to a two-dimensional rigid crystalline (or gel)
state at a characteristic freezing point – phase transition – lower if
hydrocarbons are short or have double bonds
▪ Longer hydrocarbon chains – more interactions along length
▪ Less double bonds – less kinks – hydrocarbon chains are closer – more
interactions
Acyl chain melting temperatures
No
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g
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Bacteria, yeasts and
other organisms whose temperature fluctuates with that of their environment adjust the
fatty acid composition of their membrane lipids to maintain a relatively constant fluidity
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Lipids and disease
There are many known lipid-associated diseases
• Lipid storage diseases
• Metabolic diseases
• Transport diseases
Example: Adrenoleukodystrophy (ALD) and Lorenzo’s oil
• ALD
o X-linked metabolic disorder
▪ Only boys
▪ Onset 6-10
o Build up of very long chain saturated fatty acids
o Destroys myelin sheath
o Neurological disability and death
• Preventative treatment
o Lorenzo’s oil
▪ 4:1 mixture of glycerol trioleate and glycerol trierucate
▪ Competitively inhibits VLFCA forming enzymes

Sterols
• Phospholipids
o Charged
o Neutral
• Sphingolipids
• Glycolipids
• Steroids
o Animal – cholesterol
o Yeast – ergosterol
o Plants – stigmasterol
Membrane fluidity: influence of cholesterol
In eukaryotes cholesterol also regulates membrane fluidity
...
At high concentrations (found in most eukaryotes), it prevents
the crystallisation of hydrocarbon chains, which thereby inhibits the phase transition,
making it more fluid
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Cholesterol also influences membrane fluidity
More ordered acyl chains are longer, so the membrane is thicker
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It inserts
into the bilayer with its hydroxyl group close to the polar head groups of the phospholipids
so that its rigid, plate-like steroid rings interact with and partially immobilise those regions
of the hydrocarbon chain closest to the polar head groups
...
Although cholesterol tightens
the packing of the lipids in a bilayer, it does not make membranes any less fluid
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Percentage of total lipid by weight
Red blood
Mitochondrion
Liver cell
Lipid
cell
(inner and
Endoplasmic
E
...
In
archaea, lipids usually contain 20-25 carbon-long prenyl chains instead of fatty acids, prenyl
and fatty acid chains are similarly hydrophobic and flexible
...
The plasma
membranes of most eukaryotic cells are more varied than those of prokaryotes and
archaea, not only in containing large amounts of cholesterol but also in containing a mixture
of different phospholipids
...
Some of this is due to the
variation in head groups, hydrocarbon chain lengths and desaturation of the major
phospholipid classes, but there are also many structurally distinct minor lipids
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Membranes have asymmetric lipid distributions

Lipid asymmetry:
• Asymmetric synthesis, specific lipid transport/translocation
• Minimal spontaneous flip-flop
Plasma membrane lipid asymmetry – why is it important?
• In the extracellular space
o Cell-cell interaction
▪ Glycolipids are important for the interaction with other cells and the
extracellular matrix
• In the cytosol
o Cell signalling
▪ PS in outer PM leaflet – apoptotic signal triggers phagocytosis by
macrophages
o Recruitment of proteins to the membrane

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Many proteins bind to PL head groups e
...
phosphoinositide-binding
proteins in cytosol
How are phospholipids synthesised?
• Each step is catalysed by enzymes in the ER membrane that have their active site
facing the cytosol, where all of the required metabolites are found
• When the fatty acids arrive in the ER membrane, they are activated with CoA
• Glycerol-3-phosphate acyl transferases add a fatty acid to phosphoglycerol to make
lysophosphatidate
• Glycerol-3-phosphate acyl transferase add a fatty acid to lysophosphatidate to make
phosphatidate (phosphatidic acid) which is sufficiently insoluble to stay in the lipid
bilayer, and it cannot be extracted from the bilayer by the fatty acid binding
proteins
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Lipids are transported via vesicular transport
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In ER, PC and PE rapidly (seconds – minutes) equilibrate between the two leaflets
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It involves “flippase” – protein “elusive”
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A scramblase equilibrates phospholipids between the two leaflets of the lipid bilayer
o Phospholipid synthesis adds to the cytosolic half of the bilayer
o Scramblase catalyses flipping of phospholipid molecules
o Symmetric growth of both halves of bilayer
o Different types of phospholipid are equally distributed between both halves
of the bilayer
o Moves down a concentration gradient
Energy-dependent flippases
Energy-dependent flippases couple ATP-hydrolysis to movement of lipids against a
concentration gradient, e
...
aminophospholipid translocase (PM) removes PS and PE from
the outer leaflet to the inner one, which generates PM lipid asymmetry
...
Result = exposure of
phosphatidylserine on the surface of apoptotic cells – signal for phagocytic cells to
ingest and degrade the dead cell

Sterol asymmetry
ABC transporters are a large family of membrane transporters with an ATP Binding Cassette
...
The family includes CFTR (cystic
fibrosis membrane conductance regulator protein) and MDR1
...
Coli have a double membrane – transport ATPases
located in inner membrane – an auxiliary mechanism is used to
capture the nutrients and deliver them to the transporters
o In E

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