Biochemistry I
Lecture 26 - Membranes
Lecture 26: Membranes &
Membrane Proteins:
March 27, 2013
Proteins
O
Cholesterol
2-
O P O
Key Terms:
 Phospholipids
 Liposomes/bilayer
 Phase transition of bilayers
 Biological Membranes
 Membrane Protein Structure
Biological Membranes
Fatty Acids
OH
Phospholipids
Waxes
Triglycerides
OH
Lipid Vesicles
Phospholipids - Glycerophospholipids:
1. Head group + phosphate + glycerol + two fatty acids (acyl chains) of various types form a phospholipid.
2. Various head groups are attached to the phosphate, giving a diverse set of lipids.
3. The nomenclature indicates the type of fatty acid attached to the 1 and 2 positions of glycerol as well as the
type of head group on the phosphate.
Head group(-X)
none
Choline
(-C-C-N+(CH3)3)
Serine (linkage via sidechain)
Name of Phospholipid
phosphatidic acid (PA)
Phosphatidylcholine (PC), called lecithin
Phosphatidylserine (PS)
Net Charge
-1
0 (zwitterion)
-1
O
H3N
+
O
P
O
glycerol
O
O
O
O
O
P
O
O
Phosphate
1
OH
2
OH
C
C
3
HO C
O
O
Glycerol
2 Fatty acids(C12-Lauric)
O
3 H2O
O
O
1-lauroyl -2-lauroyl-3-phosphatidylcholine
O
O
(dilauroyl phophatidyl choline, DLPC)
H2O
O
C
H3C
CH3
N
+
H3C
O
2
C
3
O
O
HO
H3C
O
1
C
acyl chain
H3C
O
N
+
CH3
OH
O
P
O
O
Phosphatidic acid
O
head group
Choline
O
P
O
head group
Physical Properties of Pure Lipid Bilayers:
1. Phospholipids self-assemble in water to form bilayers (two opposing layers of phospholipids). Bilayers are
formed instead of micelles because the cross section of the head group is roughly equal to the cross section of
the 2 fatty acid chains found in phospholipids.
2. The bilayers form closed, water filled, vesicles with a 40-50 Å thick wall. The non-polar acyl chain width is
about 30 Å.
3. Permeability properties:
 Charged compounds do not cross the bilayer.
 Polar ones infrequently.
 Non-polar ones readily.
O
O
P
O
O
O
O
O
O
=
Chemical
structure
Simplified
representation
Section of bilayer
Phospholipid
vesicle
1
Biochemistry I
Lecture 26 - Membranes
March 27, 2013
Phase transition:


The effect of chain length and cis-double bonds on
TM is due to van der Waals packing.
DMPC (C14) = 23 C
DPPC (C16) = 41 C
DSPC (C18) = 58 C
DOPC (C18:1) = -22 C
O
1.2
1
Fraction Fluid

Phospholipid Melting(DPPC)
Lipid bilayers undergo a highly
cooperative (melts over a narrow temp
range) phase transition with a defined
Tm:
Below Tm the lipids exist as a solid-like
gel; the acyl chains are tightly packed.
Above Tm the lipids are in a liquid-like
liquid crystal phase. The acyl chains
are disordered. Thus the phase
transition is called the gel to liquidcrystalline transition.
Above Tm rapid lateral diffusion of
lipids and proteins occurs in the plane
of the membranes.
Choline
O
O
O
60
80
DSPC
DPPC
DMPC
DOPC
14
16
18
20
Fatty Acid Carbon Length
H HH
H
P
O
70
60
50
40
30
20
10
0
-10
-20
-30
12
O
Choline
40
PC Melting
O
O
20
Temp (C)
O
O
0.4
0
O
P
0.6
0
O
O
0.8
0.2
Temp (C)

O
O
O
Cholesterol:
1. Is a natural steroid, you produce about 1 g/day!
2. About the same length as C16 fatty acid; therefore it
reaches across half of the bilayer.
3. Essential component of most mammalian membranes.
4. Destroys the phase transition of pure lipid membranes,
thereby keeping the membranes fluid below the phase
transition and more rigid above the phase transition.
Often referred to as a membrane plasticizer.
O
O
OH
Cholesterol
Palmitic acid (C16)
2
Biochemistry I
Lecture 26 - Membranes
March 27, 2013
Peripheral Membrane Proteins:
 Loosely attached to membranes via electrostatic interactions – released
with high salt.
 Often involved in electron transport and, as specific binding proteins, e.g.
sugar transport in bacteria.
Structure of Integral Membrane Proteins:
 Largely contained within in the membrane
(solubilization requires disruption of the membrane
by detergents).
 Stability energetics are similar to water soluble
proteins, except that membrane proteins are "insideout".
i. Non-polar groups interact with acyl chains in the
membrane. The general rule here is: hydrophobic
outside--hydrophilic or hydrophobic inside,
depending on function.
ii. Virtually all hydrogen bonds for residues within the
bilayer must be satisfied because there is no water
available. Loss of these hydrogen bonds in the
folded form costs +25kJ/mol, leading to instability
of the folded form if they are not reformed when
the protein inserts into the membrane. Acceptable
secondary structures are:
-barrel
-helix

Top-View
X-section
Usually, the secondary structures are amphipathic, displaying a nonpolar face to the lipids and a polar face to the interior of the protein.
The polar groups in the interior are responsible for function.
Energetics of Membrane Insertion: Non-polar side chain must
provide sufficient energy to overcome the unfavorable energy of +1
kcal/mol that is required to bury polar mainchain atoms in the non-polar
environment.
The overall transfer energy for glycine is +1.0, alanine +0.5, and valine
-0.6 kcal/mol-residue.
CH3
H H
+1.0 kcal/
mol-residue
N
H
O
N
H
O
H3C
N
H
CH3
O
3
Biochemistry I
Lecture 26 - Membranes
March 27, 2013
Biological Membranes – Fluid mosaic model.
Peripheral Membrane Proteins:
 Often involved in electron transport and, as specific binding proteins, e.g. sugar transport in bacteria.
Integral Membrane Proteins:
1. Transport (e.g. of protons, metabolites, electrons)
a. Passive transport (no energy required, molecules spontaneously go from high concentration to low)
b.Active transport (energy required, molecules are pushed from low to high concentration.)
2. Signal transduction.
3. Enzymes.
HO
HO
HO
Bacteriorhodopsin
K+ Channel:
Light activated proton-pump:
converts light to energy!
Osmotic Effects;

A concentration difference across a membrane represents a system that is not at
equilibrium.
 Water will flow across the membrane to establish equal concentration on both
sides of the membrane.
 Flow of water through the lipid bilayer is slow.
 Presence of aquaporin (water channel) increases the rate at which equilibrium
is reached.
 Ions will not flow across the membrane, unless a channel is present.
Hypertonic solution: The concentration of
salt is higher outside the cell than inside
the cell.
Isotonic solution: The concentration of salt
is the same inside and outside the cell.
Hypotonic solution: The concentration of
salt is lower outside the cell than inside
the cell.
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