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Module BIO00004C
Molecular Biology and Biochemistry
Lectures 17-18Christoph Baumann([email protected])
Introduction to Lipids and Membranes
Learning OutcomesAt the end of these lectures you should know:
what is a membrane lipid
what is a neutral lipid
basic structural features of fatty acids, phospholipids, glycolipids,
sphingolipids and cholesterol why lipids self-assemble to form membranes
basics of biological membrane structure and dynamics
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mitochondria / chloroplasts
nuclear envelope
endoplasmic reticulum
Golgi complex
peroxisomes
lysosomes
vesicles
Eukaryotic Cells Have Internal Membranes Too
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Chemical Composition of Purified Membranes
02476Mitochondrial innermembrane
02575Halobacteriumpurplemembrane
03070Chloroplast membrane
44254ameoba
45244mouse liver
84349human erythrocyte
Plasma membrane:
37918Myelin
CarbohydrateLipidProteinMembrane type
Percentage by Weight
Guidotti (1972) Ann. Rev. Biochem. 41: 731
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Membranes are sheet-like structures
Consist of lipids, proteins and carbohydrates
Membranes are formed from lipids with hydrophobic and hydrophilic moieties
Specific proteins give distinct functions
Membranes are non-covalent structures held together by many interactions
Membranes are asymmetric (outer leaflet / inner leaflet)
Membranes are fluid structures (rapid 2D diffusion)
Most cell membranes are electrically polarised
Common Features Underlie
the Diversity of Biological Membranes
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Soap Bubble as a Model Membrane Bilayer
Air
Hydrophobic tails
Hydrophilic headgroups
Water
Ionicdetergentmolecules
Detergent molecules are amphipathic both polar and non-polar properties
Air
Hydrophobic tails
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Fatty Acids are Key Constituents of Membrane Lipids
Ability of membrane lipids to form
bilayeris due to their hydrophobicproperties
Hydrophobic properties are due tofatty acid hydrocarbon tails
Fatty acids spontaneously form amicellein water, not a bilayer
Micelle
16 carbons (saturated)
18 carbons1 cisdouble-bond(unsaturated)
Numbering carbonsin fatty acid chain
Double-bond positionsin fatty acid chain
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Isomerism in Unsaturated Fatty Acids
Free Rotation of C-C Bond in Saturated Fatty Acids
C CC C
~109
anti gauche
CH3
CH3
H
HH
H
CH3CH
3
H
H
HH
18 carbons and 1 double-bondC18:118:1!9or 18:1!11
Positional isomerism:18 carbons and 2 double-bondsC18:2
18:2!9,12or 18:2!6,9
Geometrical isomerism: C Ccis
H H
R1 R2
C Ctrans
R1 H
H R2
~120
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C18:0 stearic acid
C18:1!9 oleic acid
C18:2!9,12 linoleic acid
C18:3!9,12,15
linolenic acid
cis
cis
cis
cis
cis
cis
9
9
12
12
15
9
"-3
"-6
"-9
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palm kernel oil
oil of nutmeg
palm oil
beef fat
olive oil
whale oil
soybean oil, safflower oil
fish oils, linseed oil
liver
Source
peanut oil
short
chainessential
fattyacids
Arachidonic acid (20:4, "-6), eicosapentaenoic acid (20:5, "-3)and docosahexaenoic acid (22:6, "-3) made from EFAs
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Neutral Lipids
Cholesterol esters
Triglyceride 3 fatty acids
Diglyceride 2 fatty acids
Monoglyceride 1 fatty acid
O
CH3
CH3
H3C CH3
CH3
R
O
esterlinkage
esterlinkage
1
2
3
numberingofcarbons
inglycerolbackbone
These molecules do not have amphipathic properties.
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Three Common Types ofMembrane Lipids
Cholesterol
Phospholipids
Glycolipids
Fattyacid
Sphingosine Phosphate Alcohol
Sugar
Fattyacid
Sphingosine Phosphate Sugar
R
HO
Polar
Polar
Polar
Polar
Polar
Non-polarNon-polar
Non-polar
HO
CH3
CH3
H3C CH3
CH3
glycophospholipid ceramide
glycosphingolipid
1
1
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Alcohols Linked to Phosphoglycerides
Common Phosphoglycerides
in Membranes
esterlinkage
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Sphingomyelin - a phospholipid containing sphingosine
Cerebroside - a glycolipid containing sphingosine
Gangliosidescontain branched polysaccharide chains with up to seven sugars
amidelinkage
amidelinkage
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O-antigenspecific
polysaccharide
Corepolysaccharide
Lipid A
LipopolysaccharidesLipoteichoic acid(e.g. Salmonella typhimurium)(e.g. Gram positive bacteria)
P
GlycerolGlcNAc
P
GlycerolD-Ala
P
GlycerolGlcNAc
Lipid
P
GlycerolD-Ala
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Bacterial cell envelope / PeptidoglycanGram positiveStaphylococcus aureus
Lipid bilayermembrane
Peptidoglycan
(cell wall)Polysaccharidecoat
Lipoteichoic acid
MurNAc
GlcNAc
Tetrapeptide(Gly)5
MurNAc
Gram negativeEscherichia coli
Cross-linkedTetrapeptides
Periplasmicspace
Lipid bilayermembrane
Peptidoglycan
Outer lipidmembrane
MurNAc
GlcNAc
MurNAc
Lipopolysaccharide
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Examples of Glycolipids
O O
O OSiaGlcGal
GalGanglioside GM1
Ceramide
O O
O
GlcNAc
Gal
L-Fuc
L-Fuc
OGalNAc
OGalNAc
O O
O
GlcNAc
Gal
O O
O
GlcNAc
Gal
L-Fuc
O
Gal
Blood group antigens
H (group 0)
A
B
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Archaeal Membranes
Contain Ether Lipids
Membrane lipid fromMethanococcus jannaschii
O
H3C
CH3
CH3
H3C
H
CH3
H3C
H
H
CH3
H
CH3
H3C
H
H3C
H
H2C C CH2
O
O
P
O
CH2
H2C
NH3
OO
H
O
P
OX
O
O
O
P
OX
O
O
O
P
OX
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
OO
Sugars
Sugars
Sugars
H
H
H
H
H
H
etherlinkage
diether glycolipids diether phospholipids
X = H, glycerol, glycerol-P-OMe, inositol, ethanolamine, serine
tetraether phosphoglycolipid
tetraether phosphoglycolipid with cyclopentane rings
Extreme halophilesMesophilic methanogens
ThermoacidophilesThermophilic methanogens
Thermoacidophiles
Extremophiles
Three Domains of Life
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Phospholipids and Glycolipids
Readily Form Membrane Bilayers in Water
Liposome is a lipid vesicle
Membrane bilayer
Membrane lipids
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Organisation of Phospholipids in Biological Membranes
Membrane bilayer asymmetry is maintainedbecause phospholipid flip-flopoccurs very,
very, very slowly
Molecular Cell Biology(6thedition, Lodish et al.) Chapter 10
Molecular shape of lipids determines
physical properties of the membrane
LPC = lysophosphatidylcholine
headgroup
non-polartail
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Phase Transitions in Lipid Bilayers
Solid- or gel-like consistency Fluid-like consistency
At constant temperature:
Increases in cholesterol or saturated fatty acid content make a membrane bilayer
more solid- or gel-like
Decreases in fatty acid chain length or increases in unsaturated fatty acid contentmake a membrane bilayer more fluid-like
Increasein
temperature
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Permeability of the Membrane Bilayer
Gases O2, CO2, N2
Small, polar and uncharged urea, ethanol
Water H2O
Large, polar and uncharged glucose
Ions Na+, K+, Mg2+, Ca2+
Cl-, HCO3-, HPO4
2-
Polar and charged amino acids
nucleotides (ATP)
glucose 6-phosphate