Module BIO00004C Molecular Biology and Biochemistry Lectures 17-18 Christoph Baumann (christoph.baumann@york.ac.

uk)

Introduction to Lipids and Membranes

Learning Outcomes
At 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

Lipids and Membranes

Boundaries of cells are formed by biological membranes: define inside and outside of the cell selectively permeable to small molecules dynamic and fluid structures composed of lipids (self-assembling) and proteins (function)
outside

inside

Eukaryotic Cells Have Internal Membranes Too

mitochondria / chloroplasts nuclear envelope endoplasmic reticulum Golgi complex peroxisomes lysosomes vesicles

Chemical Composition of Purified Membranes

Percentage by Weight Membrane type Myelin Plasma membrane:
human erythrocyte mouse liver ameoba

Protein 18 49 44 54 70 75 76

Lipid 79 43 52 42 30 25 24

Carbohydrate 3 8 4 4 0 0 0

Chloroplast membrane

Halobacterium purple membrane

Mitochondrial inner membrane

Guidotti (1972) Ann. Rev. Biochem. 41: 731

Common Features Underlie the Diversity of Biological Membranes

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

Soap Bubble as a Model Membrane Bilayer

Air Hydrophobic tails Hydrophilic headgroups Water Ionic detergent molecules

Hydrophobic tails Air

Detergent molecules are amphipathic both polar and non-polar properties

Fatty Acids are Key Constituents of Membrane Lipids

Ability of membrane lipids to form bilayer is due to their hydrophobic properties Hydrophobic properties are due to fatty acid hydrocarbon tails Fatty acids spontaneously form a micelle in water, not a bilayer
18 carbons 1 cis double-bond (unsaturated) 16 carbons (saturated)

Double-bond positions in fatty acid chain Numbering carbons in fatty acid chain

Micelle

Free Rotation of C-C Bond in Saturated Fatty Acids

C
~109

H H

CH3

H H

anti

H H

CH3

CH3 H

gauche

CH3

Isomerism in Unsaturated Fatty Acids

18 carbons and 1 double-bond C18:1 18:1!9 or 18:1!11 18 carbons and 2 double-bonds C18:2 18:2!9,12 or 18:2!6,9
H H R1 H

Positional isomerism:

Geometrical isomerism:
R1

cis

C ~120
R2 H

trans

C
R2

C18:0
cis
9

stearic acid oleic acid

C18:1!9

"-9

cis
9

C18:2!9,12

linoleic acid

cis 12

"-6

cis cis 12 cis

15

C18:3!9,12,15 linolenic acid

"-3

Source palm kernel oil oil of nutmeg palm oil beef fat peanut oil

whale oil olive oil

short chain essential fatty acids

soybean oil, safflower oil fish oils, linseed oil liver

Arachidonic acid (20:4, "-6), eicosapentaenoic acid (20:5, "-3) and docosahexaenoic acid (22:6, "-3) made from EFAs

Neutral Lipids
ester linkage

numbering of carbons in glycerol backbone

Triglyceride Diglyceride Monoglyceride

3 fatty acids 2 fatty acids 1 fatty acid

1 2

These molecules do not have amphipathic properties.

H3C CH3 CH3 CH3

Cholesterol esters
O

ester linkage

CH3

Three Common Types of Membrane Lipids

1

Phospholipids
Non-polar

Polar

Fatty acid Sphingosine

Polar
Phosphate Alcohol

Non-polar
1

Glycolipids
Polar
HO

Polar
Sugar

Fatty acid Sphingosine

Polar
Phosphate Sugar

glycophospholipid

ceramide glycosphingolipid

H3C

CH3 CH3

Non-polar

CH3 CH3

Cholesterol
R
HO

Alcohols Linked to Phosphoglycerides

ester linkage

Common Phosphoglycerides in Membranes

Sphingomyelin - a phospholipid containing sphingosine

amide linkage

Cerebroside - a glycolipid containing sphingosine

amide linkage

Gangliosides contain branched polysaccharide chains with up to seven sugars

Lipoteichoic acid
(e.g. Gram positive bacteria)

Lipopolysaccharides
(e.g. Salmonella typhimurium)
O-antigen specific polysaccharide Core polysaccharide

P D-Ala Glycerol P GlcNAc Glycerol P D-Ala Glycerol P GlcNAc Glycerol

Lipid A

Lipid

Bacterial cell envelope / Peptidoglycan

Gram positive Staphylococcus aureus
Peptidoglycan Polysaccharide (cell wall) coat Lipoteichoic acid MurNAc GlcNAc MurNAc

Lipid bilayer membrane

Tetrapeptide

(Gly)5

Gram negative Escherichia coli

Lipopolysaccharide Outer lipid membrane Periplasmic space MurNAc GlcNAc MurNAc

Peptidoglycan

Lipid bilayer membrane

Cross-linked Tetrapeptides

Examples of Glycolipids
GalNAc
O

#
O

Ceramide

Gal
O

Glc

Gal

Sia GlcNAc
O

Ganglioside GM1

Gal
O

H (group 0)

$
GlcNAc
O

L-Fuc GalNAc
O

Gal
O

$
GlcNAc
O

Blood group antigens

L-Fuc
O

Gal

Gal
O

L-Fuc

Archaeal Membranes Contain Ether Lipids

NH3 H2C CH2 O O O H2C P O H C O CH2 O

Three Domains of Life

ether linkage Extreme halophiles Mesophilic methanogens

H Sugars O

O P O OX O

diether glycolipids

diether phospholipids
O

O P

H H3C

CH3 H

Thermoacidophiles Thermophilic methanogens

H Sugars O

OX O

O O

O O

H H3C

CH3 H

tetraether phosphoglycolipid
O

H H3C

CH3 H

Thermoacidophiles Extremophiles
H Sugars O

O
O O O O H

OX O

H3C CH3 H3C

CH3

tetraether phosphoglycolipid with cyclopentane rings X = H, glycerol, glycerol-P-OMe, inositol, ethanolamine, serine

Membrane lipid from Methanococcus jannaschii

Phospholipids and Glycolipids Readily Form Membrane Bilayers in Water

Liposome is a lipid vesicle

Membrane lipids

Membrane bilayer

palmitic acid

O
H3N

Vesicle
O H H2C O C O

CH2 H2C O P O CH2 O O

Bilayer is 5-10 nanometers thick

dipalmitoylphosphatidylcholine (DPPC)

Organisation of Phospholipids in Biological Membranes

Molecular shape of lipids determines physical properties of the membrane

headgroup non-polar tail

Membrane bilayer asymmetry is maintained because phospholipid flip-flop occurs very, very, very slowly

LPC = lysophosphatidylcholine

Molecular Cell Biology (6th edition, Lodish et al.) Chapter 10

Phase Transitions in Lipid Bilayers

Solid- or gel-like consistency Fluid-like consistency

Increase in temperature

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 content make a membrane bilayer more fluid-like

Permeability of the Membrane Bilayer

Gases Small, polar and uncharged O2, CO2, N2 urea, ethanol

Water

H2O

Large, polar and uncharged

glucose

Ions

Na+, K+, Mg2+, Ca2+ Cl-, HCO3-, HPO42-

Polar and charged

amino acids nucleotides (ATP) glucose 6-phosphate