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Module BIO00004C

Molecular Biology and Biochemistry

Lectures 17-18Christoph Baumann(christoph.baumann@york.ac.uk)

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