Tymoczko • Berg • Gatto • Stryer

Biochemistry: A
Short Course
Fourth Edition

CHAPTER 12
Membrane
Structure and
Function

© 2019 Macmillan Learning

 CHAPTER 12
Membrane Structure and Function
 Chapter 12: Outline

12.1 Phospholipids and Glycolipids Form Bimolecular

Sheets
12.2 Membrane Fluidity Is Controlled by Fatty Acid
Composition and Cholesterol Content
12.3 Proteins Carry Out Most Membrane Processes
12.4 Lipids and Many Membrane Proteins Diffuse
Laterally in the Membrane
12.5 A Major Role of Membrane Proteins Is to Function as
Transporters
 Characteristics of Membranes
1. Membranes are sheetlike structures, two molecules thick, that form
closed boundaries.
2. Membranes are composed of lipids and proteins, either of which can
be decorated with carbohydrates.
3. Membrane lipids are small amphipathic molecules that form closed
bimolecular sheets that prevent the movement of polar or charged
molecules.
4. Proteins serve to mitigate the impermeability of membranes and
allow movement of molecules and information across the cell
membrane.
5. Membranes are noncovalent assemblies.
6. Membranes are asymmetric in that the outer surface is always
different from the inner surface.
7. Membranes are fluid structures.
8. Most cell membranes are electrically polarized such that the inside is
negative.
 Section 12.1 Phospholipids and
Glycolipids Form Bimolecular Sheets
Learning objective 1: Identify the energetic force that
powers the formation of membranes.

• Phospholipids and glycolipids form lipid bilayers in

aqueous solutions.
• The formation of membranes is powered by the
hydrophobic effect.
 Electron Micrograph and Space-filling
Model of a Phospholipid Bilayer Membrane
 Clinical Insight: Lipid Vesicles Can Be
Formed from Phospholipids
CLINICAL INSIGHT
Lipid Vesicles Can Be Formed from
Phospholipids

• Liposomes, or lipid vesicles, are aqueous compartments

enclosed by a lipid membrane.
• Liposomes, formed by sonicating a mixture of
phospholipids in aqueous solution, may be useful as
drug-delivery systems. The advantage of drug delivery
by liposomes is that the drugs are more targeted than
are systemic drugs, which means that less of the body is
exposed to potentially toxic drugs.
Diagram of a Liposome
Diagram of the Preparation of Glycine-
Containing Liposomes
 Lipid Bilayers Are Highly Impermeable to
Ions and Most Polar Molecules
Learning objective 2: Explain why membranes are
impermeable to most substances.
Lipid bilayers are highly impermeable to ions and most polar molecules.
• The ability of small molecules to cross a membrane is a function of
its hydrophobicity.
• Indole is more soluble than tryptophan in membranes because it is
uncharged. Ions cannot cross membranes because of the energy
cost of shedding their associated water molecules.
Permeability Coefficients of Ions and
Molecules in a Lipid Bilayer
 Section 12.2 Membrane Fluidity Is
Controlled by Fatty Acids Composition
and Cholesterol Content
• Membrane processes depend on the fluidity of the
membrane.
• The temperature at which a membrane transitions from
being highly ordered to very fluid is called the melting
temperature.
• The melting temperature is dependent on the length of the
fatty acids in the membrane lipid and the degree of cis
unsaturation.
• Cholesterol helps to maintain proper membrane fluidity in
membranes in animals.
 Graph of the Phase-transition, or Melting,
Temperature for a Phospholipid Membrane
Diagram of the Packing of Saturated Fatty
Acid Chains in a Membrane
 Diagram of the Packing of Saturated and
Unsaturated Fatty acid Chains in a Membrane
Diagram of Cholesterol Disrupting the
Tight Packing of Fatty Acid Chains
 Quick Quiz 1

QUICK QUIZ 1
Predict the effect on membrane lipid
composition if the temperature of a bacterial
culture is raised from 37°C to 42°C.
 Section 12.3 Proteins Carry Out Most
Membrane Processes
Learning objective 3: Describe the roles of proteins in
making membranes selectively permeable.
• Although membrane lipids establish a permeability
barrier, membrane proteins allow transport of
molecules and information across the membrane.
• Membranes vary in protein content from as little as
18% to as much as 75%.
 Proteins Associate with the Lipid Bilayer
in a Variety of Ways (1/2)
Proteins associate with the lipid bilayer in a variety of ways.
• Integral membrane proteins are embedded in the
hydrocarbon core of the membrane.
• Peripheral membrane proteins are bound to the polar head
groups of membrane lipids or to the exposed surfaces of
integral membrane proteins.
• Some proteins are associated with membranes by
attachment to a hydrophobic moiety that is inserted into
the membrane.
Diagram of Integral and Peripheral
Membrane Proteins
 Proteins Associate with the Lipid Bilayer
in a Variety of Ways (2/2)
• Membrane-spanning α helices are a common structural
feature of integral membrane proteins.
• Other means of embedding integral membrane proteins is
by using β strands to form a pore in the membrane or by
embedding part of the protein into the membrane.
Structure of Bacteriorhodopsin
Structure of Bacterial Porin
 Clinical Insight: The Association of
Prostaglandin H2 Synthase-I with the
Membrane Accounts for the Action of Aspirin
CLINICAL INSIGHT
The Association of Prostaglandin H2
Synthase-I with the Membrane Accounts for
the Action of Aspirin

• The cyclooxygenase (COX) activity of prostaglandin H2

synthase-1 is dependent on a channel connecting the
active site to the membrane interior.
• Aspirin inhibits cyclooxygenase activity by obstructing the
channel.
 Diagram of the Attachment of
Prostaglandin H2 synthase-1 to the
Membrane
Structure of the Hydrophobic Channel of
Prostaglandin H2 synthase-1.
Diagram of Aspirin’s Effects on
Prostaglandin H2 synthase-1
 Section 12.4 Lipids and Many Membrane
Proteins Diffuse Laterally in the
Membrane
• Fluorescence recovery after photobleaching (FRAP) is a
technique that allows the measurement of lateral mobility of
membrane components.
• A membrane component is attached to a fluorescent molecule.
On a very small portion of the membrane, the dye is
subsequently destroyed by high-intensity light, thereby
bleaching a portion of the membrane.
• The mobility of the fluorescently labeled component is a function
of how rapidly the bleached area recovers fluorescence.
• Lateral diffusion of proteins depends on whether they are
attached to other cellular or extracellular components.
Diagram of the Technique of Fluorescence
Recovery After Photobleaching
 Transverse Diffusion
• Lipids rapidly diffuse laterally in membranes, although
transverse diffusion or flip-flopping is very rare without the
assistance of enzymes.
• The prohibition of transverse diffusion accounts for the
stability of membrane asymmetry.
Diagram of Lipid Movement in
Membranes
 Section 12.5 A Major Role of Membrane
Proteins Is to Function as Transporters
• A small molecule will spontaneously cross a membrane if two
conditions are met:
1. The concentration of the molecule is higher on one side of
the membrane than the other.
2. The molecule is lipophilic or soluble in nonpolar solutions.
• Molecules meeting these criteria can simply diffuse across the
cell membrane.
• Polar molecules can diffuse across a membrane down their
concentration gradient only with the assistance of a particular
protein called a channel. Such movement is called facilitated
diffusion or passive transport.
• Movement of molecules against a concentration gradient
requires a source of energy and is called active transport.
 Transport Proteins
• Transport proteins function as pumps or channels to
facilitate the flow of small molecules across the cell
membrane.
• Passive transport or facilitated diffusion occurs when a
molecule moves down its concentration gradient through a
transport protein.
• Protein pumps use energy to move a molecule against its
concentration gradient in the process of active transport.
 The Na+–K+ ATPase Is an Important Pump
in Many Cells
• The Na+–K+ ATPase or Na+–K+ pump
uses the energy of ATP hydrolysis to
simultaneously pump three Na+ ions
out of the cell and two K+ ions into the
cell against their concentration
gradients.
• Because the reaction includes an
intermediate in which the enzyme is
phosphorylated, such pumps are
called P-type ATPases.
Diagram of Energy Transduction by
Membrane Proteins
 Clinical Insight: Multidrug Resistance
CLINICAL INSIGHT
Multidrug Resistance Highlights a
Family of Membrane Pumps with ATP-
Binding Domains

• Another prominent class of membrane pumps is the

ABC transporters, so named because they all contain a
domain that binds ATP, called the ATP-binding cassette.
• Members of this class include the multidrug-resistance
protein, which pumps drugs out of a cell, and the cystic
fibrosis transmembrane conductance regulator, which
acts as a chloride channel. Mutations in this protein lead
to cystic fibrosis.
Diagram of ABC transporters (1/2)
Diagram of ABC transporters (2/2)
 Clinical Insight: Harlequin Ichthyosis
CLINICAL INSIGHT
Harlequin Ichthyosis Is a Dramatic Result of
a Mutation in an ABC Transporter Protein

• Harlequin ichthyosis is a severe pathological

condition that results from a mutation in an ABC
transporter in a common type of skin cell.
 Secondary Transporters Use One Concentration
Gradient to Power the Formation of Another

Secondary transporters use one concentration gradient to power

the formation of another.
• Symporters power the transport of a molecule against its
concentration gradient by coupling the movement to the
movement of another molecule down its concentration gradient,
with both molecules moving in the same direction.
• Antiporters also use one concentration gradient to power the
formation of another, but the molecules move in opposite
directions.
• Glucose is moved into some animal cells against its
concentration gradient by a symporter that is powered by Na+
ions moving down a concentration gradient.
Diagram of Antiporters and Symporters
Diagram of Secondary Transport
 Clinical Insight: Digitalis
CLINICAL INSIGHT
Digitalis Inhibits the Na+–K+ Pump by
Blocking Its Dephosphorylation

• Cardiotonic steroids such as

digitalis strengthen heart
contractions and are used to treat
heart disease.
• One means of removing Ca2+ from
the cell is by a Na+/Ca2+
antiporter. By inhibiting the Na+–
K+ ATPase, Ca2+ ions remain in
the cell longer, leading to a more
robust heart contraction.
• Digitalis is isolated from the
foxglove plant Digitalis purpurea.
DID YOU KNOW?
Interestingly, digitalis was used effectively long
before the discovery of the Na+–K+ ATPase. In
1785, William Withering, a British physician,
heard tales of an elderly woman, known as “the
old woman of Shropshire,” who cured people of
“dropsy” (which today would be recognized as
congestive heart failure) with an extract of
foxglove. Withering conducted the first scientific
study of the effects of foxglove on congestive
heart failure and documented its effectiveness.
Image of Foxglove
 Specific Channels Can Rapidly Transport
Ions Across Membrane
• Ion channels are passive transport systems that allow
specific and rapid transport of ions down their
concentration gradients.
• Channels can be activated by changes in the voltage
across a membrane (voltage-activated channels) or by
binding of specific molecules to the channels (ligand-
activated channels).
• Tetrodotoxin, produced by the pufferfish, is a lethal inhibitor
of the Na+ channel.
Image of a Pufferfish
Structure of Tetrodotoxin
 Biological Insight: Venomous Pit Vipers
BIOLOGICAL INSIGHT
Venomous Pit Vipers Use Ion Channels to
Generate a Thermal Image

• Transient receptor potential (TRP) channels play a variety of

roles in animals. Venomous pit vipers use TRP channels to
generate a thermal image that is overlaid on their visual image
to assist in hunting.
 The Structure of the Potassium Ion Channel
Reveals the Basis of Ion Specificity
The structure of the potassium ion channel reveals the basis
of ion specificity.
• The potassium channel selectively and rapidly transports
K+ across the cell membrane. Larger ions are not
transported because they are too big to enter the channel.
• Smaller ions are excluded because they cannot interact
with the selectivity filter. Such ions are small enough that
the energy of desolvation cannot be compensated for by
interactions with the selectivity filter.
Diagram of a Path Through a Channel
Diagram of the Selectivity Filter of the
Potassium Ion Channel
Diagram of the Energetic Basis of Ion
Selectivity
The Structure of the Potassium Ion Channel
Explains Its Rapid Rate of Transport
• Charge repulsion among the four ion binding sites in the
potassium channel accounts for the rapid transport of K+
ions down their concentration gradient.
• Two different models—the Hard-Knock model and the
Knock-On model—have been proposed, and both depend
on charge repulsion as the driving force for rapid ion
movement.
A Model for K+-channel Transport
 Quick Quiz 2

QUICK QUIZ 2
What determines the direction of flow
through an ion channel?
 APPENDIX: Biochemistry in Focus (1/2)
Action potentials are mediated by transient changes in Na+
and K+ permeability
• A nerve impulse is an electrical signal
produced by the flow of ions across the
plasma membrane of a nerve cell or
neuron from the dendrites to the terminal
bulb.
• A nerve impulse, or action potential, is
generated when the membrane potential
is depolarized beyond a critical threshold
value. The membrane potential becomes
positive within about a millisecond before
turning negative again. This amplified
depolarization is propagated along the
axon. Action potentials arise from large,
transient changes in the permeability of
the neuron membrane to Na+ and K+ ions.
 APPENDIX: Biochemistry in Focus (2/2)
Action potentials are mediated by transient changes in Na+
and K+ permeability
• Direct evidence for the existence of the ion channels in
neurons was provided by the patch-clamp technique.
 APPENDIX: Problem-Solving Strategies 1

PROBLEM:
Two different species of bacteria have been isolated
from two different environments: a geothermal spring
and a glacial lake. In a geothermal spring, water
temperatures approach 40°C (104°F), whereas the
temperature of a glacial lake can be as low as 4°C
(39.2°F). How would the lipid composition of the
membranes differ between the two species?
 APPENDIX: Problem-Solving Strategies 1
Solution (1/3)
SOLUTION:
Let’s begin by reviewing what functions membranes perform.
What are the key functions of membranes?
• The lipid components of membranes provide a permeability
barrier and an environment for membrane proteins, which allow
selective permeability. That is, proteins allow transport of
specific biochemicals into and out of the cell.
The problem involves bacteria living at two different temperature
extremes. To see how lipid composition might differ, let’s perform a
thought experiment. Let’s imagine a typical bacterium growing at
20°C. Suppose we then quickly raised the temperature to 40°C.
 APPENDIX: Problem-Solving Strategies 1
Solution (2/3)
SOLUTION:
What would be the effect of the temperature on the membrane?
• There would be an increase in membrane fluidity because of increased
Brownian motion due to the rise in temperature. Too much fluidity would result
in the loss of a permeability barrier as the lipids wiggled around, and
membrane proteins would cease to function because of the disrupted lipid
environment.
Now let’s image our typical 20°C bacterium is quickly moved to a 4°C
environment.
How would the membrane respond to a fall in environmental temperature?
• The lower temperature would decrease membrane fluidity. In an extreme case,
the membrane lipids would solidify. Recall from our earlier discussion of
proteins that protein structure is dynamic as the proteins perform their various
functions. The loss of lipid fluidity would compromise protein function.
 APPENDIX: Problem-Solving Strategies 1
Solution (3/3)
SOLUTION:
The fact that bacteria can live in geothermal springs and glacial lakes suggests
that bacteria can alter their membrane lipids to meet environmental needs. So
geothermal springs bacteria must prevent too much fluidity and glacial lake
bacteria must maintain adequate fluidity by altering the membrane lipid
composition.
What changes in lipid composition would decrease membrane fluidity? Increase
membrane fluidity?
• To decrease fluidity, the geothermal spring bacteria would incorporate long
saturated fatty acids into the membrane lipids. The long chains would allow
increased van der Waals interactions between the chains and prevent excess
fluidity. Now how is it possible to prevent too much lipid packing that would
decrease fluidity in the glacial lake bacteria? The lipid chain would be shorter,
reducing van der Walls interactions. Also, cis-double bonds would be
introduced into the lipids. Recall that these double bonds cause a kink in the
hydrocarbon chain of the lipids, thereby reducing packing and increasing
fluidity.
 APPENDIX: Problem-Solving Strategies 2

PROBLEM:
The uptake of glucose by two different cell types is shown
below. The figure shows rate of glucose uptake for each
cell type in the presence of increasing amounts of sodium.
What do these results reveal about the glucose transporter
in each cell type?
 APPENDIX: Problem-Solving Strategies 2
Solution (1/3)
SOLUTION:
First, as always when we look at data,
we need to know what we are actually
looking at.
What information is displayed on the y
axis? And on the x axis?
• The y axis shows glucose uptake,
while the x axis shows sodium
concentration. In other words, the
graph shows glucose uptake in two
types of cells as a function of
sodium concentration.
 APPENDIX: Problem-Solving Strategies 2
Solution (2/3)
SOLUTION:
How does the glucose uptake in the two different
cell types respond to increases in sodium
concentration?
• Glucose uptake by cell type 1 is independent
of sodium concentration. That is, changing the
sodium concentration has no effect on glucose
uptake. On the other hand, glucose uptake in
cell type 2 increases as sodium concentration
increases in a hyperbolic fashion. By analogy
to enzyme activity, the hyperbolic curve for
type 2 cells suggests the involvement of a
protein in the transport of glucose.
 APPENDIX: Problem-Solving Strategies 2
Solution (3/3)
SOLUTION:
Thinking back about the transport systems
discussed in this chapter, can you answer the
following question?
What type of transport system is catalyzing the
uptake of glucose in a sodium-dependent fashion
in cell type 2?
• Most likely a sodium-dependent secondary
transport system since glucose transport
requires sodium (p. 233).
What can we conclude about the transport
system of cell type 1?
• Nothing really, except that glucose transport is
independent of sodium concentration.