Notesale: Turn your study into money

Document Preview

Extracts from the notes are below, to see the PDF you'll receive please use the links above

---

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
...

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
...

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

▪

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
...

Lipids are transported via vesicular transport
...


•
•
•
•
•

In ER, PC and PE rapidly (seconds – minutes) equilibrate between the two leaflets
...

It involves “flippase” – protein “elusive”
...

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
...
falciparum amplified a gene encoding an ABC
transporter that pumps out chloroquine
• Cystic fibrosis (mutated CFTR – cystic fibrosis transmembrane conductance regulator
protein)
o Discovered through studies of cystic fibrosis
o Mutation in CFTR – functions as a Cl- channel in the plasma membrane of
epithelial cells
o CFTR regulates ion concentrations in the extracellular fluid, especially in the
lungs
o 1/27 Caucasians carries a gene encoding a mutant form of this protein
o 1/2900, both copies of the gene are mutated – this causes the disease
o In contrast to other ABC transporters, ATP binding and hydrolysis do not
drive the transport process – instead, control the opening and closing of Cl-,
which provides a passive conduit for Cl- to move down its electrochemical
gradient
• Tangier disease (mutated ABCA1)
o Orange tonsils, enlarged liver and spleen
o Mediates efflux of cholesterol from cytosolic to outer leaflet of PM
o Disease leads to accumulation of cholesterol in cells
• Sitosterolaemia (mutated ABCG5 and ABCG8)
o Increased intestinal sterol absorption
o Decreased secretion of sterol into bile
o ABC mediate sterol uptake and efflux
Mitochondria, peroxisomes and plastids
• Not connected to ER via vesicular transport system
• No de novo lipid synthesis, therefore lipids are transported from the ER
• Monomeric diffusion of lipids is energetically unfavourable
...

• Animal cells synthesise phosphatidylserine and phosphatidylcholine in the
endoplasmic reticulum and then transfer them to the outer membrane of
mitochondria
...
Mitochondria and plastids are not part of this system and therefore require
different mechanisms to import lipids and proteins for growth

•

o They import most of their proteins from the cytosol
o They do not synthesise lipids de novo – their lipids are imported from the ER
So how do lipids get from the ER to other organelles? By lipid transfer proteins

Phospholipid exchange proteins
Lipids are insoluble in

---