Chapter 12
Lipids and Cell Membranes
The surface of a soap
bubble is a bilayer formed
by detergent molecules.
The polar heads(red) pack
together, leaving the
hydrophobic groups(green).
The boundaries of the cells =
Biological membranes (the
barriers that define the inside
and the outside of a cell).
Prevent molecules leaking out
and unwanted molecules from
diffusing in.
Allow the cell to take up
specific molecules and remove
unwanted ones.
Internal membranes :
mitochondria, chloroplasts,
peroxisomes, lysosomes…
Many common features underlie the diversity of biological
membranes
1. Membranes are sheetlike structures, only two molecules
thick.(60Å~100Å)
2. Membranes consist of lipids and proteins.
3. Membrane lipids are small molecules that have both
hydrophilic and hydrophobic moieties.
4. Specific proteins mediate distinctive functions of
membranes (pumps, channels, receptors, energy
transducers and enzymes).
5. Membranes are noncovalent assemblies.
6. Membranes are asymmetric.
7. Membranes are fluid structures.
8. Most cell membranes are electrically polarized.
12.1 Fatty acids are key constituents of lipids
Fatty acid names are based on their parent hydrocarbons
-Fatty acid : long hydrocarbon chains of various lengths and
degrees of unsaturation terminated carboxylic acid groups.
-Fatty acid name is derived from the name of its parent
hydrocarbon.
-Ex> C18 saturated fatty acid = octadecanoic acid (18:0)
parent hydrocarbon = octadecane
C18 with one double bond = octadecenoic acid(18:1)
C18 with two double bond = octadecadienoic acid(18:2)
C18 with three double bond = octadecatrienoic acid(18:3)
16:0
18:1
- Fatty acid carbon atoms are
numbered starting at the carboxyl
terminals.
-Carbon atom 2 = α
-Carbon atom 3 = β
-Methyl carbon atom at the distal
end of the chain = ω-carbon atom
-The position of double bond = Δ
-Ex> cis-Δ9 = cis double bond between
carbon 9 and 10.
-Double bond counting from the distal
end = ω-carbon as number1.
-Ex> ω-3
Fatty acids vary in chain length and degree of unsaturation
-16~18 carbon fatty acid are most common.
-The properties of fatty acid and of lipids derived from them
are dependent on chain length and degree of saturation.
※ Unsaturated fatty acid = lower melting points
saturated fatty acid = higher melting points (same length)
12.2 There are three common types of membrane
lipids
※ Three major kinds of membrane lipids
1.Phospholipids
2.Glycolipids
3.Cholesterol
※ Lipids have a variety of biological roles :
1.Fuel molecules.
2.Signal molecules and messengers in signal transduction.
3.Components of membranes.
Phospholipids are the major class of membrane lipids
-One or more fatty acids
-Platform to which the
fatty acids are attached
-Phosphate
-alcohol
-Phospholipids are abundant in all
biological membranes.
- Composed with 4 components.
-Platform are built may be glycerol, a
three carbon alcohol, or sphingosine.
-Phosphoglyceride : phospholipid derived from glycerol.
-C1 and C2 are esterified to the carboxyl groups of the two
fatty acid chains.
-C3 hydroxyl group is esterified to phosphoric acid.
-When no more addition → the simplest fatty acid,
phosphatidate
They can be attached
to phosphate group as
alcohol moieties.
- Sphingomyelin : backbone is sphingsine(amino alcohol that
contains a long, unsaturated hydrocarbon chain).
-The amino group of the sphingosine bachbone is linked to a
fatty acid by amide bond.
-The primary hydroxyl group is esterified to
phosphorylcholine.
Membrane lipids can include carbohydrate moieties
-Glycolipid : sugar containing lipid.
-Derived from sphingosine.
-Amide group is acylated by a fatty acid.
-Primary hydroxyl group is linked to one or more sugars.
-Sugar residues always on the extracellular side of the
membrane.
Cholesterol is a lipid based on a steroid nucleus
-Cholesterol : a lipid with different structure.
steroid, built from four linked hydrocarbon rings.
Hydrocarbon
Hydroxyl group
-Only found in virtually all animal membranes.
-Almost 25% of the membrane lipids in nerve cell.
-Absent from some intracellular membranes.
Archaeal membranes are built from ether lipids with branched
chains
- Archaea membranes differ from
eukaryotes or bacteria
membranes.
1.Nonpolar chains are joined to a
glycerol backbone by ether than
ester linkages.(ether is more
resistant to hydrolysis)
2.Alkyl chains are
branched.(branched chain is more
resistant to oxidation)
3.Stereochemistry of the central
glycerol is inverted.
A membrane lipid is an amphipathic molecule containing a
hydrophilic and a hydrophobic moiety
-Membrane lipids are amphipathic.
-Contains both a hydrophilic and
hydrophobic moiety.
-Overall shape : rectangular.
-Polar head : hydrophilic, red circle.
-Hydrocarbon chain : hydrophobic,
straight or wavy lines.
12.3 Phospholipids and glycolipids readily form
bimolecular sheets in aqueous media
-Polar head groups favor contact with
water, hydrocarbon chains interact with
one another.
-Micelle : globular structure.
-Lipid bilayer : two lipid sheets.
-A micelle is a limited structure (less than
200Å in diameter)
-Bimolecular sheet can extend to
millimeter or more.
-Lipid bilayers are held together by many
noncovalent interactions (hydrophobic),
Idealized view
they are cooperative structures.
-Hydrophobic interactions have three
significant biological consequences.
1. Extensive
2. Close on themselves (no edges)
3. Self-sealing (no holes)
Realistic view
Lipid vesicles can be formed from phospholipids
-Lipid vesicles, or liposomes are aqueous compartments
enclosed by a lipid bilayer.
-Can be used to study membrane permeability or to deliver
chemicals to cells.
-Liposomes are formed by suspending
a suitable lipid, such as
phosphatidylcholine, in an aqueous
medium.
-Sonicating
-Vesicles formed.(diameter of about
500Å)
-Ions or molecules can be trapped in
the vesicles.
-Molecule containing vesicles can be
separated by dialysis or gel
filtration chromatography.
-A bilayer membrane is formed across a 1-mm hole in a
septum that separates two aqueous compartments.
-This arrangement permits measurements of the
permeability and electrical conductance of lipid bilayers.
Lipid bilayers are highly impermeable to ions and most polar
molecules
1/109
-Lipid bilayer membranes have a very low permeability for
ions and most polar molecules. Why?
-Na+ and K+ traverse the membranes 109 times as slowly as
does H2O.
12.4 Proteins carry out most membrane processes
-Specific proteins mediate membrane functions.
-Membranes differ in their protein
contents.
-Ex> Myelin(nerve fiber) = 18%
Plasma membrane = 50%
Energy transduction
membrane(mitochondria and
chloroplast) = 75%
- Membranes contains many
proteins, but has a distinct protein
composition.
Proteins associate with the lipid bilayer in a variety of ways
- Integral membrane protein : interact with the
hydrocarbon chains of membrane lipids(a, b, and c). Can
be released by a detergent or an organic solvent.
- Peripheral membrane protein : bound to membranes
primarily by electrostatic and hydrogen bond interactions
with the head groups of lipid(d and e). Can be released by
adding salts or changing the pH.
Proteins can span the membrane with alpha helices
-Bacteriorhodopsin : uses light energy to transport protons
from inside the cell to outside → proton gradient.
-Almost α helices; 7 closely packed α helices.
-Span its 45Å width.
-Examination of the primary structure of
bacteriorhodopsin : most of the amino acid in α helices are
nonpolar(yellow) and only a very few are charged(red).
-Membrane-spanning α helices are the most common
structural motif in membrane proteins.
A channel protein can be formed from beta strands
-Porin : built from β strands and contain essentially no
α helices.
-Each strand is hydrogen bonded to its neighbor in an
antiparallel arrangement.
-The outside surface of porin is nonpolar. Interact
with the hydrocarbon chains.
-The inside of the channel is hydrophilic and is filled
with water.
-Alternation of hydrophobic and hydrophilic amino
acids along each β strand. Why?
-Hydrophobic – yellow
Embedding part of a protein in a membrane can link the
protein to the membrane surface
- Prostaglandin H2 synthase-1 : catalyzes the conversion of
arachidonic acid into prostaglandin H2 in two steps.
1. Cyclooxygenase reaction
2. Peroxidase reaction
- Prostaglandin H2 promotes
inflammation and modulates
gastric acid secretion
- Lies along the outer surface of the membrane firmly
bound by a set of α helices with hydrophobic surfaces
that extend from the bottom of the protein into the
membrane.
- Partially embedded.
-The location of prostaglandin H2 synthase-1 in the membrane
is crucial to its function.
-The substrate(arachidonic acid) : hydrophobic, generated by
the hydrolysis of membrane lipids.
-The substrate reaches the active site through a hydrophobic
channel(yellow).
-Drug(aspirin) block the channel.
(by transfer acetyl group to Ser530)
Membrane proteins: all alpha helix or beta sheet?
Some proteins associate with membranes through covalently
attached hydrophobic groups
Palmitoyl group attached to a
cystein by a thioester bond.
Farnesyl group attached to a
cystein at the carboxyl terminus.
mannose
GlcNAc
By enzymes
Glycosylphosphatidylinositol(GPI)
anchor attached to the carboxyl
terminus.
Transmembrane helices can be accurately predicted from
amino acid sequences
Phe : hydrophobic amino acid.
unfavorable(+15.5kJ/mol)
Arg : positively charged amino acid.
favorable(-51.7kJ/mol)
30Å ≈ 20 residues
-Window : the span of 20 residues chosen for this calculation.
-The free energy change for each window is plotted against
the first amino acid at the window to create a hydropathy plot.
- ≥80kJ/mol in a hydropathy plot : membrane spanning α helix.
- Some membrane proteins contain membrane-spanning
features that escape detection by these plot.
12.5 Lipids and many membrane proteins diffuse
rapidly in the plane of the membrane
-Lateral diffusion : lipids and many membrane proteins are
in lateral motion.
- FRAP(fluorescence recovery after photobleaching)
1. Cell-surface component is labeled with a fluorescent chromophore.
2. A small region is viewed through a fluorescence microscope.
3. Fluorescent molecules in this region are destroyed by laser.
4. This region is monitored.
5. Bleached molecules leave and unbleached molecules enter.
6. Recover the fluorescent intensity in this region.
-The rate of recovery depends on the lateral mobility of
the component, which can be expressed in terms of a
diffusion coefficient, D.
-The average distance S = (4Dt)1/2
-Rhodopsin ‘s D = 0.4μm2/s
-Fibronectin’s D = 10-4μm2/s (because it is anchored to
actin filaments on the inside of the plasma membrane
through integrin.)
The fluid mosaic model allows lateral movement but not
rotation through the membrane
-Fluid mosaic model : membranes are two-dimensional solutions of
oriented lipids and globular proteins.
- lipid bilayer’s roles
: a solvent for integral membrane proteins.
: a permeability barrier.
-The lateral diffusion can be rapid.
-The transition of a molecule from
one membrane surface to the other
is very slow = transverse diffusion
or flip-flop.
Membrane fluidity is controlled by fatty acid composition
and cholesterol content
-Membrane transport or signal transduction depend to the
fluidity of the membrane lipids.
- The transition from rigid to
the fluid state takes place
rather abruptly as the
temperature is raised above
Tm, the melting temperature.
-Tm depends on the length of the fatty acid chains and on
their degree of unsaturation.
-A cis double bond produces a bend in the hydrocarbon
chain. This bend interferes with a highly ordered packing
of fatty acid chains, and so Tm is lowered.
-Bacteria regulate the fluidity of their membranes by
varying the number of double bonds and length of fatty
acid chains
-In animals, Cholesterol is the key regulator of membrane
fluidity, (hydroxyl group : phospholipid head group,
hydrocarbon tail : nonpolar core of the bilayer)
-Cholesterol disrupts the interactions between fatty acid
chain increasing the membrane fluidity.
-Cholesterol forms specific complexes with some
phospholipids to make lipid rafts
All biological membranes are asymmetric
-Membranes are structurally and functionally asymmetric.
-Different component and enzymatic activity between
outer and inner membrane.
※ Na+ - K+ PUMP
-Na+ out of the cell.
-K+ into the cell.
12.6 Eukaryotic cells contain compartments
bounded by internal membranes
Protection
Plasma membrane
Permeability barrier
-Gram negative bacteria
(E.coli)
-When staining, pink color
-Double membrane
-Thin cell wall (peptidoglycan)
between them.
-LPS (lipopolysaccharide)
-Small molecules permeable
due to porin
-Gram positive bacteria and
archaea.
-When staining, violet color
-Single membrane surrounded by
cell wall (thick peptidoglycan
layer)
-Eukaryotic cells are
distinguished from prokaryotic
cells by the presence of
membranes inside the cell that
form internal compartments.
(peroxisome, mitochondria,
nucleus)
- Membranes must be able to separate or join together so
that cells and compartments may take up, transport, and
release molecules.
- Invaginated membrane
Breaks off and fuses to
form a vesicle.
- The vesicle containing
the LDL fuses with a
lysosome→ degradation.
- Many cells take up molecules
through the process of receptormediated endocytosis.
- Hormones, antibodies, transport
proteins
※ LDL receptor : recycled.
※Cholesterol and amino acid :
store or use
※ virus and toxin also use
receptor-mediated endocytosis
Iron is essential but Free iron
ions are toxic because of free
radical formation.
Special transport is necessary
- The reverse process (the fusion of a vesicle to a
membrane) is a key step in the release of neurotransmitters
from a neuron into the synaptic cleft.