7 | Carbohydrates and

Glycobiology

© 2017 W. H. Freeman and Company

CHAPTER 7
Carbohydrates and Glycobiology

Learning goals:
• Structures and names of monosaccharides
• Open‐chain and ring forms of monosaccharides
• Structures and properties of disaccharides
• Biological function of polysaccharides
• Biological function of glycoconjugates

1
 Carbohydrates
• Named so because many have formula Cn(H2O)n
• Produced from CO2 and H2O via photosynthesis in plants
• Exist as monomers (monosaccharides) or oligosaccharides)
– Disaccharide: two monosaccharides
– Polysaccharides: 20+ monosaccharides
• Fulfill a variety of functions, including:
– energy source and energy storage
– structural component of cell walls and exoskeletons
– informational molecules in cell‐cell signaling
• Can be covalently linked with proteins and lipids
– Glycoprotein: major component of protein
– Proteoglycan‐major component sugar (polysaccharide + amino sugars)

Carbohydrates

• Basic nomenclature:
– number of carbon atoms in the carbohydrate +
‐ose
– example: three carbons = triose
• Common functional groups:
– All carbohydrates initially had a carbonyl
functional group.
– aldehydes = aldose
– ketones = ketose

2
Two families of monosaccharides: aldoses and ketoses

• An aldose is a carbohydrate with aldehyde functionality.

• A ketose is a carbohydrate with ketone functionality.

Seliwanoff’s test: https://www.youtube.com/watch?v=zA2DIuJqbyU

Carbohydrates Can Be Stereoisomers

• Enantiomers
– stereoisomers that are
nonsuperimposable mirror images
chiral
• In sugars that contain many chiral center
centers, only the one that is most
distant from the carbonyl carbon is
designated as D (right) or L (left).
• D and L isomers of a sugar are
enantiomers.
– For example, L‐ and D‐glucose have the
same water solubility.
• Most hexoses in living organisms are D
stereoisomers.
• Some simple sugars occur in the L form, • Aldoses (‐CHO)
• Ketoses (‐C=O)
such as L‐arabinose.

3
 Drawing Monosaccharides

• Chiral compounds can be

D L drawn using perspective
formulas.
• However, chiral
carbohydrates are usually
represented by Fischer
projections.
D L • Horizontal bonds are
pointing toward you;
vertical bonds are
projecting away from you.

Nomenclature of monosaccharides
• A molecule with n chiral centers can have 2n stereoisomers.
• Glyceraldehyde has 21 = 2; the aldohexoses, with four chiral
centers, have 24 = 16.
• Only the one that is most distant from carbonyl carbon is used to
designate the sugar as D (right) or L (left).
•Hydroxyl group on the reference carbon is on the
right (dextro) in a projection formula that has the
carbonyl carbon at the top, the sugar is the D
isomer; when on the left (levo), it is the L isomer.
‐OH right‐ ‐OH left‐
•The carbons of a sugar are numbered beginning at not
handed handed
chiral oriented oriented
the end of the chain nearest the carbonyl group.

4
 Diastereomers

• Diastereomers: stereoisomers that are not mirror

images (not an enantiomer).
• Diastereomers have different physical properties.
– For example, water solubilities of threose and erythrose are
different.

Note: In a sugar molecule

larger than three carbons, we
have more than an One hydroxyl
enantiomer to consider, group is
because we have more than switched
one chiral carbon.

they are not enantiomers of each other

Epimers
When you get even more carbons present…………..

• Epimers (type of diastereomer) are two sugars that differ only

in the configuration around one carbon atom.
• D‐Mannose and D‐galactose are both epimers of D‐glucose.
• D‐Mannose and D‐galactose vary at more than one chiral center
and are diastereomers, but not epimers.2

Note: Each epimer differs

from D‐glucose in the
configuration at one chiral
center (shaded light red or
blue).

5
6
No D or L configuration

7
Most monosaccharides exist as cyclic strutures
• Aldehyde and ketone carbons are electrophilic.
• Alcohol oxygen atom is nucleophilic.
• When aldehydes are attacked by alcohols, hemiacetals form.
• When ketones are attacked by alcohols, hemiketals form.
• These reactions form the basis of cyclization of sugars.
electrophilic Nucleophilic
carbon oxygen

Nucleophilic attack

electrophilic Nucleophilic
carbon oxygen

Nucleophilic attack

Hemi groups are precursors of cyclic structures Essential to establish glycosidic bonds

Cyclization of
Nucleophilic
attack from the
alcohol to the alcohol attack to
Monosaccharides
aldehyde group C‐5
• Pentoses and hexoses easily
nucleophilic attack
undergo intramolecular
from alcohol to C1 cyclization
electrophilic – Most common form in water
carbon • The former carbonyl carbon
becomes a new chiral center
two
as a hydroxyl group, called the
hemiacetals anomeric carbon.
– If the hydroxyl group is on the
trans cis opposite side (trans) of the ring
as the CH2OH the configuration
is α.
– If the hydroxyl group is on the
same side (cis) of the ring as the
CH2OH, the configuration is β.

8
 Cyclization of Anomeric
Anomeric
carbon
Monosaccharides: carbon

Pyranoses and Furanoses

• Six‐membered oxygen‐
containing rings are Anomeric
Anomeric carbon
called pyranoses after carbon
the pyran ring structure.
• Five‐membered oxygen‐
containing rings are
called furanoses after
the furan ring structure.
• The anomeric carbon is
usually drawn on the
right side.

Conformational Formulas of Cyclized

Monosaccharides
• Cyclohexane rings have “chair” or “boat” conformations.
• Pyranose rings favor “chair” conformations.
• Multiple “chair” conformations are possible but require energy
for interconversion (~46 kJ/mole).

9
Converting Fisher projections to Haworth
perspective formula
• Number the carbons in a clockwise direction
beginning with the anomeric carbon, then
place the hydroxyl groups.
• If a hydroxyl group is to the right it is place
pointing down; if it is to the left, it is placed
pointing up.
• The terminal –CH2OH group projects upward
for the D‐enantiomer, downward for the L‐
enantiomer.
• The hydroxyl on the anomeric carbon can
point up or down. When the anomeric
hydroxyl is on the same side of the rings as C‐
6, β; when it is on the opposite side, α.

Important Hexose Derivatives important in biology

In amino sugars, an —NH2

group replaces one of the —
OH groups in the parent
hexose. Substitution of —H
for —OH produces a deoxy
sugar; note that the deoxy
sugars shown here occur in
nature as the L isomers. The
acidic sugars contain a
carboxylate group, which
confers a negative charge at
neutral pH. D-Glucono-δ-
lactone results from
formation of an ester linkage
between the C-1 carboxylate
group and the C-5 (also
known as the δ carbon)
hydroxyl group of D-
gluconate.

10
 The Glycosidic Bond
• Two sugar molecules can be joined via a
glycosidic bond between an anomeric
carbon and a hydroxyl carbon.
• The glycosidic bond (an acetal) between
monomers is more stable and less reactive
than the hemiacetal at the second
monomer.
– The second monomer, with the hemiacetal, is
reducing.
– The anomeric carbon involved in the
glycosidic linkage is nonreducing.
• Disaccharides can be named by the
organization and linkage or a common name.
– The disaccharide formed upon condensation
of two glucose molecules via a 1  4 bond is
described as α‐d‐glucopyranosyl‐(14)‐d‐
glucopyranose.
– The common name for this disaccharide is
maltose.

The Glycosidic Bond: Maltose

hemiketal
or
Formation of maltose. A disaccharide
is formed from two monosaccharides
(here, two molecules of D-glucose)
when:
1. an —OH (alcohol) of one glucose
molecule (right) condenses with
the intramolecular hemiacetal of
the other glucose molecule (left),
with elimination of H2O and
formation of a glycosidic bond.
2. The reversal of this reaction is
hydrolysis—attack by H2O on the
glycosidic bond.

11
 Naming Disaccharides
1. Nonreducing end to the left
2. Give the configuration (α or β) at he anomeric carbon joining the first
monosaccharide unit (on the left) to the second.
3. Name the nonreducing residue; to distinguish five-and six-membered ring
structures, insert “furano” or “pyrano” into the name.
4. Indicate in parentheses the two carbon atoms joined by the glycosidic bond, with
an arrow connecting the two numbers
5. Name the second residue. If there is third residue, describe the second glycosidic
bond by the same conventions.

α‐glucopyranosyl (1→2) β fructofuranoside

or
α glucose (1→2) β fructose

Nonreducing Disaccharides
• Two sugar molecules can be
also joined via a glycosidic
bond between two anomeric
carbons.
• The product has two acetal
groups and no hemiacetals.
• There are no reducing ends;
this is a nonreducing sugar.

12
 Polysaccharides
• Natural carbohydrates are usually found
as polymers.
• These polysaccharides can be:
– homopolysaccharides (one monomer
unit)
– heteropolysaccharides (multiple
monomer units)
– linear (one type of glycosidic bond)
– branched (multiple types of glycosidic
bonds)
• Polysaccharides do not have a defined
molecular weight.
– This is in contrast to proteins because,
unlike proteins, no template is used
to make polysaccharides.
– Polysaccharides are often in a state of
flux; monomer units are added and
removed as needed by the organism.

Glycogen a Polysaccharide

• Glycogen is a branched
homopolysaccharide of glucose.
– Glycosidic bonds of glucose
monomers to form (1  4) linked
chains.
– There are branch points with (1 
6) linkers every 8–12 residues.
– Molecular weight reaches several
millions.
– It functions as the main storage
polysaccharide in animals.

13
 Homopolymers of Glucose:
Starch
• Starch is a mixture of two homopolysaccharides of glucose.
• Amylose is an unbranched polymer of (1  4) linked residues.
• Amylopectin is branched like glycogen, but the branch points with (1
 6) linkers occur every 24–30 residues.
• Molecular weight of amylopectin is up to 200 million.
• Starch is the main storage polysaccharide in plants.

Strands of amylopectin
(black) form double‐
helical structures with
each other or with
amylose strands (blue).

Metabolism of Glycogen and Starch

• Glycogen and starch are insoluble due to their high molecular

weight and often form granules in cells.
• Granules contain enzymes that synthesize and degrade these
polymers.
– Fortunately, we have enzymes that breakdown α linkage
• Glycogen and amylopectin have one reducing end but many
nonreducing ends.
– therefore, it is very easy to add and remove glucose as necessary
• Enzymatic processing occurs simultaneously in many
nonreducing ends.

14
 Homopolymers of Glucose:
Cellulose
• Cellulose is a linear homopolysaccharide of glucose.
– Glucose monomers form (1  4) linked chains.
• As humans, we don’t have enzymes to break β 1→4 linkages.
– Hydrogen bonds form between adjacent monomers.
– There are additional H‐bonds between chains.
– Structure is now tough and water insoluble.
– It is the most abundant polysaccharide in nature.
– Cotton is nearly pure fibrous cellulose.

Cellulose Metabolism
• Most animals cannot use cellulose as a fuel source because they
lack the enzyme to hydrolyze (1 4) linkages.
• The fibrous structure and water insolubility make cellulose a
difficult substrate to act upon.
• Fungi, bacteria, and protozoa secrete cellulase, which allows
them to use wood as source of glucose.
• Ruminants and termites live symbiotically with microorganisms
that produce cellulase and are able to absorb the freed glucose
into their bloodstreams.
• Cellulases hold promise in the fermentation of biomass into
biofuels.

15
 Glycoconnjugates
• In addition to fuel
storage and structural
roles, polysaccharides
carry information.
– Cell‐cell communication
– Protein labeling
– Recognition sites fro signal
molecules

• Often exists as a
glycoconjugates
(carbohydrate + protein
or lipid) or proteoglycan
(glycosaminoglycan chain
+ protein)
– Information rich carbohydrate layer
surrounding cells (glycocalix)

İzzetoğlu S, Turkish Journal of Biology 38:754‐771

Glycosaminoglycans
• Linear polymers of repeating
disaccharide units
• One monomer is either:
– N‐acetyl‐glucosamine or
– N‐acetyl‐galactosamine
• The other it will be negatively
charged
– uronic acids (C6 oxidation)
– sulfate esters
• Extended hydrated molecule
– minimizes charge repulsion
• Forms meshwork with fibrous
proteins to form extracellular
matrix
– connective tissue
– lubrication of joints Newburg et al., 2014 May;75(5):675‐9
Human milk

16
• Hyaluronate
• Synovial fluid
• Vitreous humor

Note: negative charges

allow a lot of water
interaction

• Chondroitin sulfate
• Cartilage
• Tendon
• Ligaments
• Aorta

Note: negative charges

allow a lot of water
interaction

• Keratan sulfate
• Cornea
• Bones
• Dead cells

• Heparin
• Binds to an
enzyme to
inhibit blood
clotting

17
 Glycoconjugates: Proteoglycans

• Sulfated glucoseaminoglycans
attached to a large rod‐shaped
protein in cell membrane
– syndecans: protein has a
single transmembrane
domain
– glypicans: protein is
anchored to a lipid
membrane
– interact with a variety of
receptors from neighboring
cells and regulate cell growth

18
 Proteoglycan Aggregates
• Our tissues have many different core
proteins; aggrecan is the best
studied.
• Hyaluronan and aggrecan form huge
(Mr > 2 • 108) noncovalent
aggregates.
• They hold a lot of water (1000 its
weight) and provide lubrication.
• Very low friction material
• Covers joint surfaces: articular
cartilage
– reduced friction
– load balancing

Glycoconjugates: Glycoprotein
• A protein with small O‐linked = anomeric C linked to Ser/Thr

oligosaccharides
attached
– Carbohydrate attached via its
anomeric carbon to Ser/Thr.
– About half of mammalian N‐linked = anomeric C linked to Asn
proteins are glycoproteins.
– Carbohydrates play role in
protein‐protein recognition.
– Only some bacteria glycosylate
a few of their proteins.
– Viral proteins are heavily
glycosylated; this helps evade
the immune system.

19
 Glycoconjugates: Analysis

Separation and quantification of the oligosaccharides in a group of glycoproteins. In this experiment, the
mixture of proteins extracted from kidney tissue was treated to release oligosaccharides from
glycoproteins, and the oligosaccharides were analyzed by matrix assisted laser desorption/ionization mass
spectrometry (MALDI MS). Each distinct oligosaccharide produces a peak at its molecular mass, and the
area under the curve reflects the quantity of that oligosaccharide. The most prominent oligosaccharide
here (mass 2837.4 u) is composed of 13 sugar residues; other oligosaccharides, containing as few as 7 and
as many as 19 residues, were also resolved by this method. Note: N‐Acetylglucosamine (GlcNAc)

Chapter 7: Summary

In this chapter, we learned about:

• structures of some important monosaccharides

• structures and properties of disaccharides
• structures and biological roles of polysaccharides
• functions of glycosylaminoglycans as structural
components of the extracellular matrix
• functions glycoconjugates in regulating a variety of
biological functions

20
 To do………

• Problems:
– #2 (page 275),
– #4, #5, #14, #15 (page 276),
– #25 (Page 277)
• Read: Boxes 7‐1, 7‐2, and 7‐3

21
 10| Lipids

© 2017 W. H. Freeman and Company

CHAPTER 10
Lipids

Learning goals:
• Biological roles of lipids
• Structure and properties of storage lipids
• Structure and properties of membrane lipids
• Structure and properties of signaling lipids

1
 Lipids: Structurally Diverse Class
Glycerol and triacylglycerol

Sphingolipids
Stearic
acid

Ubiquinone
Cholesterol

Organic molecules that are characterized by low

solubility in water, that is, are relatively hydrophobic.

Biological Functions of Lipids

• Storage of energy
– reduced compounds: lots of available energy
– hydrophobic nature: good packing
• Insulation from environment
– low thermal conductivity
– high heat capacity (can “absorb” heat)
– mechanical protection (can absorb shocks)
• Water repellant
– hydrophobic nature: keeps surface of the organism dry
• prevents excessive wetting (birds)
• prevents loss of water via evaporation
• Buoyancy control and acoustics in marine mammals
– increased density while diving deep helps sinking (just a hypothesis)
– spermaceti organ may focus sound energy: sound stun gun?

2
 More Functions
• Membrane structure
– main structure of cell membranes
• Cofactors for enzymes
– vitamin K: blood clot formation
– coenzyme Q: ATP synthesis in mitochondria
• Signaling molecules
– paracrine hormones (act locally)
– steroid hormones (act body‐wide)
– growth factors
– vitamins A and D (hormone precursors)
• Pigments
– color of tomatoes, carrots, pumpkins, some birds
• Antioxidants
– vitamin E

Lipids Can Provide Pigment

Compounds with long conjugated systems absorb light in the visible region of the spectrum. Subtle differences in the
chemistry of these compounds produce pigments of strikingly different colors. Birds acquire the pigments that color their
feathers red or yellow by eating plant materials that contain carotenoid pigments, such as canthaxanthin and zeaxanthin.

3
 Classification of Lipids
Two major categories based on the structure and
function:
1.Lipids that contain fatty acids (complex lipids)
– can be further separated into:
• storage lipids and membrane lipids
2. Lipids that do not contain fatty acids: cholesterol, vitamins,
pigments, etc.

Fatty Acids
• Carboxylic acids with hydrocarbon chains containing between
4 to 36 carbons
– Almost all natural fatty acids have an even number of carbons.
– Most natural fatty acids are unbranched.
• Saturated: no double bonds between carbons in the chain
• Monounsaturated: one double bond between carbons in the
alkyl chain
• Polyunsaturated: more than one double bond in the alkyl
chain

4
 Fatty Acid Nomenclature
• Standard nomenclature
• For monounsaturated:
• #1 assigned to carboxyl carbon
• ∆n = site of double bond
• Polyunsaturated fatty acid (PUFA) alternative:
• #1 assigned to terminal methyl carbon
• Ѡ (omega) – n = site of double bond
Description:
18 = carbons Monounsaturated
1 = one double bond
∆9 = site double bond
starts
Cis: geometry of double
bond
‐9‐ = site were cis occur Polyunsaturated
Octa = fatty acid with 18
carbons omega carbon

EPA: an essential Fatty Acid

• Omega‐3 fatty acids are essential nutrients.
– Humans need the essential PUFA‐α‐linolenic acid (ALA).

5
 Solubility and Melting Point
of Fatty Acids
• Solubility
– decreases as the chain length
increases (i.e., saturated fatty
acids)

• Melting Point
– decreases as the chain length
decreases
– decreases as the number of
double bonds increases (i.e.,
unsaturated fatty acids)

Conformation of Fatty Acids

• The saturated chain tends to adopt extended conformations.
• The double bonds in natural unsaturated fatty acids are
commonly in cis configuration, which kinks the chain.

6
 Melting Point and Double Bonds
• Saturated fatty acids pack in a fairly orderly way.
– extensive favorable interactions
• Unsaturated cis fatty acids pack less orderly due to the kink.
– less‐extensive favorable interactions
• It takes less thermal energy to disrupt disordered packing of
unsaturated fatty acids.
– Unsaturated cis fatty acids have a lower melting point.

Trans Fatty Acids

• Trans fatty acids form by partial dehydrogenation of
unsaturated fatty acids.
– done to increase shelf life or stability at high temperature
of oils used in cooking (especially deep frying)
• A trans double bond allows a given fatty acid to
adopt an extended conformation.
• Trans fatty acids can pack more regularly and show
higher melting points than cis forms.
• Consuming trans fats increases risk of cardiovascular
disease (dietary trans fats can raise level of LDL and
lower HDL).
– Avoid deep frying partially hydrogenated vegetable oils.
– Current trend: reduce trans fats in foods (Wendy’s, KFC).

7
 Triacylglycerols (Nonpolar)
• The majority of fatty acids in
biological systems are found in
the form of triacylglycerols.
– Solid ones are called fats.
– Liquid ones are called oils.
• The primary storage form of
lipids (body fat)
• Less soluble in water than
fatty acids due to the
esterification of the
carboxylate group
• Less dense than water: fats
Glycerol and a triacylglycerol. The mixed triacylglycerol shown here has
and oils float. three different fatty acids attached to the glycerol backbone. When
glycerol has different fatty acids at C‐1 and C‐3, C‐2 is a chiral center.

Fats Provide Efficient Fuel Storage

• The advantage of fats over
polysaccharides:
– Fatty acids carry more energy per
carbon because they are more
reduced.
– Fatty acids carry less water per gram
because they are nonpolar.
• Glucose and glycogen are for short‐term
energy needs and quick delivery.
• Fats are for long‐term (months) energy
needs, good storage, and slow delivery.
– The human being can be up to three
(a) Cross section of human white adipose tissue.
days without consuming any food,
Each cell contains a fat droplet (white) so large the energy stored in fats will be used.
that it squeezes the nucleus (stained red) against
the plasma membrane.

8
 Structural Lipids in Membranes (Polar)
• Contain polar head groups and nonpolar tails (usually
attached fatty acids)
• Diversification can come from:
• modifying a different backbone
• changing the fatty acids
• modifying the head groups
● The properties of head groups determine the

charged al physiological pH
surface properties of membranes.

Phosphate groups are

● Different organisms have different membrane lipid
head group compositions.
● Different tissues have different membrane lipid
head group compositions.

General Structure of Glycerophospholipids (or

Phosphoglycerides)

• Unsaturated fatty acids are commonly found connected to C2 of

glycerol‐3‐phosphate.
• The highly polar phosphate group may be further esterified by an
alcohol; such substituent groups are called the head groups.

1
2 3

Note: study Figure 10‐8

9
 Examples of Glycerophospholipids

(structural parent for all glycerophospholipids)

Phosphatidylcholine
• Phosphatidylcholine is the major component of most
eukaryotic cell membranes.
• Many prokaryotes, including E. coli, cannot synthesize
this lipid; their membranes do not contain
phosphatidylcholine.

10
 Ether Lipids: Platelets‐Activating Factor
• Aliphatic ether analog of phosphatidylcholine
• Acetic acid has esterified position C2
• First signaling lipid to be identified
• Stimulates aggregation of blood platelets
• Plays role in mediation of inflammation

Sphingolipids
• The backbone of sphingolipids is
NOT glycerol.
• The backbone of sphingolipids is a
long‐chain amino alcohol
sphingosine (a primary alcohol).
• A fatty acid is joined to sphingosine
via an amide linkage, rather than an (structural parent for all sphingolipids)

ester linkage as usually seen in

lipids.
• A polar head group is connected to
sphingosine by a glycosidic or
phosphodiester linkage.
• The sugar‐containing
glycosphingolipids are found largely
in the outer face of plasma
membranes.

11
 Sphingomyelin
• Ceramide (sphingosine + amide‐linked fatty acid) +
phosphocholine attached to the alcohol
• Sphingomyelin is abundant in myelin sheath that
surrounds some nerve cells in animals.

amide bond

Glycosphingolipids and Blood Groups

• The blood groups are determined in part by the type

of sugars located on the head groups in
glycosphingolipids.
• The structure of sugar is determined by an expression
of specific glycosyltransferases.
– Individuals with no active glycosyltransferase will have the O
antigen (O blood group).
– Individuals with a glycosyltransferase that transfers an
N‐acetylgalactosamine group have A blood group.
– Individuals with a glycosyltransferase that transfers a
galactose group have B blood group.

12
Glycosphingolipids Determine Blood Groups

Blood Groups: AB Blood Group have two Distinct Antigens

13
 Structural and Signaling Lipids Are
Degraded in the Lysosome
• Most cells continually degrade
and replace their membrane
lipids.

• Phospholipids are degraded by

phospholipases A−D.
• Each phospholipase cleaves a
specific bond.

• Gangliosides are degraded via a

series of enzymatic cleavages.
• Failure to correctly degrade
gangliosides results in build‐up of
lipids in lysosomes, a dysfunction
categorized as “lysosomal storage
disorders.”

Dysfunction in Ganglioside Recycling

Leads to a Variety of Medical Disorders

Pathways for the breakdown of

GM1, globoside, and sphingomyelin
to ceramide. A defect in the
enzyme hydrolyzing a particular
step is indicated by X; the disease
that results from accumulation of
the partial breakdown product is
noted.

14
 Sterols and Cholesterol
• Sterol
– steroid nucleus: four fused rings
– hydroxyl group (polar head) in the A‐ring
– various nonpolar side chains
• The steroid nucleus is almost planar.

non polar
side

Physiological Role of Sterols

• Cholesterol and related sterols are present in the
membranes of most eukaryotic cells.
– modulate fluidity and permeability
– thicken the plasma membrane
– most bacteria lack sterols
• Mammals obtain cholesterol from food or synthesize
it de novo in the liver.
• Cholesterol, bound to proteins, is transported to
tissues via blood vessels.
– Cholesterol in low‐density lipoproteins (LDL) tends to
deposit and clog arteries.
• Many hormones are derivatives of sterols.
¿How does Lipitor (atorvastatin) lower cholesterol?

15
Polyketides Are Biologically Active Lipids
with Medicinal Uses
• Polyketides are a diverse family of compounds synthesized similarly to fatty acid
biosynthesis.
• commonly secondary metabolites with specialized function

Three polyketide natural products

used in human medicine.

Chapter 10: Summary

In this chapter, we learned that:
• lipids are a structurally and functionally diverse
class of molecules that are poorly soluble in
water
• triacylglycerols are the main storage lipids
• phospholipids are the main constituents of
membranes
• sphingolipids play roles in cell recognition
• cholesterol is part of the membrane lipid

16
 To do………..

• Problems #2, #3, #8 (page 385) and 16 (page

386).
• Read Box 10‐1

17
 11| Biological
Membranes and
Transport
© 2017 W. H. Freeman and Company

CHAPTER 11
Biological Membranes and Transport

Learning goals:
• The function of biological membranes
• The structure and composition membranes
• Dynamics of membranes
• Structure and function of membrane proteins
• Transport across biological membranes

1
 What Are Membranes?
• Complex lipid‐based structures
that form pliable sheets
• Composed of a variety of lipids
and proteins
• All cells have a cell membrane,
which separates the cell from
its surrounding.
• Eukaryotic cells have various
internal membranes that divide
the internal space into
compartments (i.e.,
organelles).

Functions of Membranes
• Define the boundaries of the cell
• Allow import and export
– Selective import of nutrients (e.g. lactose)
– Selective export of waste and toxins (e.g. antibiotics)
• Retain metabolites and ions within the cell
• Sense external signals and transmit information into the
cell
• Provide compartmentalization within the cell
– separate energy‐producing reactions from energy‐consuming ones
– keep proteolytic enzymes away from important cellular proteins
• Produce and transmit nerve signals
• Store energy as a proton gradient
• Support synthesis of ATP

2
 Common Features of Membranes
• Sheet‐like flexible structure, 30–100 Å (3–10 nm) thick
• Main structure is composed of two leaflets of lipids (bilayer)
– with the exception of archaebacteria: monolayer of bifunctional lipids
• Form spontaneously in aqueous solution and are stabilized
by noncovalent forces, especially hydrophobic effect
• Protein molecules span the lipid bilayer
• Asymmetric
– Some lipids are found more commonly “inside.”
– Some lipids are found more commonly “outside.”
– Carbohydrate moieties are always outside the cell.
– Electrically polarized (approx.. – 60 mV inside).
• Fluid structures: two‐dimensional solution of oriented lipids

Reminder: Hydrophobicity
• A single phospholipid
molecule = low entropy
• Forms in the solution of
amphipathic molecules that
have larger, more polar head
than tail
– fatty acids
– SDS
• Micelles are composed of a
few dozen to a few thousand
lipid molecules.
• Aggregation of individual
lipids into micelles is
concentration dependent and
is spontaneous.

3
 Membrane Bilayer
• A membrane bilayer consists of two leaflets of lipid
monolayers
– Hydrophilic head groups
interact with water on
both sides of the bilayer.
– Hydrophobic fatty acid
tails are packed inside.
– One leaflet faces the
cytoplasm.
– Another leaflet faces the
extracellular space or the
inside of membrane‐
enclosed organelle.

Vesicle (Liposome)
• Small bilayers will
spontaneously seal into
spherical vesicles in a
concentration‐dependent
manner.
• Synthetic vesicle membranes
can be made in vitro and can
contain artificially inserted
proteins.
• The central aqueous cavity can
enclose dissolved molecules.
• They are useful artificial
carriers of molecules (e.g.,
drugs).
• Vesicles fuse readily with cell
membranes or with each other.

4
 The Composition of Membranes
• Lipid composition of membranes varies by:
– organisms
– tissues
– organelles
• Ratio of lipid to protein varies
- type of phospholipid varies
- abundance and type of sterols varies
- Prokaryotes lack sterols
- cholesterol predominant in the plasma membrane, virtually absent in
mitochondria
- galactolipids abundant in plant chloroplasts but almost absent in animals

Membrane Composition Is
Highly Variable in Different Organelles

5
Membrane Bilayers
Are Asymmetric
• Two leaflets have
different lipid
compositions.
• The outer leaflet is often
more positively charged.
• Phosphatidylserine
outside has a special
meaning:
– platelets: activates
blood clotting
– other cells: marks the Phosphatidylcholine

cell for destruction

Membrane composition and asymmetry

6
 Fluid Mosaic Model of Membranes
• Proposed in 1972 by Singer and
Nicholson (UCSD)
• Lipids form a viscous, two‐
dimensional solvent into which
proteins are inserted and
integrated more or less deeply.
– Integral proteins are firmly
associated with the membrane,
often spanning the bilayer.
– Peripheral proteins are weakly
associated and can be removed
easily.
• Some are noncovalently
attached.
• Some are linked to membrane
lipids.

Functions of Proteins in Membranes

• Receptors: detecting signals from outside
– light (opsin)
– hormones (insulin receptor)
– neurotransmitters (acetylcholine receptor)
– pheromones (taste and smell receptors)
• Channels, gates, pumps
– nutrients (maltoporin)
– ions (K‐channel)
– neurotransmitters (serotonin reuptake protein)
• Enzymes
– lipid biosynthesis (some acyltransferases)
– ATP synthesis (F0F1 ATPase/ATP synthase)

7
Three Types of Membrane Proteins
• Integral membrane proteins
Integral protein – Span the entire membrane
– Require detergent to remove due
to hydrophobic interactions
• Peripheral membrane proteins
– Change ionic interactions (pH or
salt) to remove from lipid polar
head groups or peripheral
proteins.
• Amphitrophic membrane proteins
– Can electrostatically interact or be
lipid anchored
– Associated highly regulated

Integral Membrane Proteins

8
 Polar AAs
Integral Membrane
Proteins Have
Selectively Placed
Nonpolar Amino Acids
Within the Membrane
Non polar AAs
One hydrophilic domain, containing all the sugar
residues, is on the outer surface, and another
hydrophilic domain protrudes from the inner face
of the membrane. Each red hexagon represents a
tetrasaccharide (containing two Neu5Ac (sialic
acid), Gal, and GalNAc) O‐linked to a Ser or Thr
residue; the blue hexagon represents an
oligosaccharide N‐linked to an Asn residue.

Six Types of Integral Membrane Proteins

9
 Amino Acids in Membrane Proteins
Cluster in Distinct Regions
• Transmembrane segments are predominantly
hydrophobic.
• Tyr and Trp cluster at nonpolar/polar interface.
• Charged amino acids are only found in aqueous domains.

Membrane Proteins Also

Contain ‐Sheets

Three proteins of the E. coli outer membrane are shown, viewed in the plane of the membrane. FepA
involved in iron uptake, has 22 membrane spanning β strands. OmpLA, a phospholipase, is a 12‐stranded
β barrel that exists as a dimer in the membrane. Maltoporin, a maltose transporter, is a trimer; each
monomer consists of 16 β strands.

10
 Lipid Anchors
• Some membrane proteins are lipoproteins.
• They contain a covalently linked lipid molecule.
– long‐chain fatty acids
– isoprenoids
– sterols
– glycosylated phosphatidylinositol (GPI)
• The lipid part can become part of the membrane.
• The protein is now anchored to the membrane.
– reversible process
– allows targeting of proteins
– Some, such as GPI anchors are found only on the outer
face of plasma membrane.

Lipid‐linked Membrane Proteins

Extracellular

Intracellular

11
 Physical Properties of Membranes
• Dynamic and flexible structures
• Can exist in various phases and undergo phase
• Not permeable to large polar solutes and ions
• Permeable to small polar solutes and nonpolar
compounds
• Permeability can be artificially increased by
chemical treatment
– For instance, when we want to get DNA into the cell

Membrane Phases
• Depending on their composition and the temperature,
the lipid bilayer can be in gel or fluid phase
– Gel phase: individual molecules do not move around
– Fluid phase: individual molecules can move around.
• Heating causes phase transition from the gel to fluid.
• Under physiological conditions, membranes are more
fluid‐like than gel‐like.
– must be fluid for proper function

12
 Membrane Phases (cont.)
Two extreme states of bilayer
lipids. (a) In the liquid‐
ordered (Lo) state, polar head
groups are uniformly arrayed
at the surface, and the acyl
chains are nearly motionless
and packed with regular
geometry. (b) In the liquid‐
disordered (Ld) state, or fluid
state, acyl chains undergo
much thermal motion and
have no regular organization.

Organisms Can Adjust

the Membrane Composition
• Membrane fluidity is determined mainly by the fatty
acid composition and melting point.
• More fluid membranes require shorter and more
unsaturated fatty acids.
– Melting temperature decreases as double bonds are added.
– Melting temperature increases with length of saturated fatty
acids.
• At higher temperatures, cells need more long,
saturated fatty acids to maintain integrity.
• At lower temperatures, cells need more unsaturated
fatty acids to maintain fluidity.

13
 Sterols and Hopanols Increase
Membrane Rigidity and Permeability
• Cell membranes of many
eukaryotes contain sterols.
– cholesterol in animals
cholesterol
– phytosterols in plants
HO
– ergosterol in fungi

• Cholesterol fits in area formed

by kink of unsaturated fatty acid
ergosterol
HO

NH2
OH OH
O OH

OH
HO OH OH • Cell membranes of aerobic
hopanol
prokaryotes contain hopanols.

Membrane Dynamics:
Lateral Diffusion
Individual lipids undergo fast lateral diffusion within
the leaflet.

14
 Membrane Dynamics:
Transverse Diffusion
Spontaneous flips from one leaflet to another are rare
because the charged head group must transverse the
hydrophobic tail region of the membrane.

Membrane Diffusion through enzymatic reactions: Flippases

• Special enzymes: flippases, floppases, and
scrambalases‐catalyze transverse diffusion.
• Flippases and floppases use energy of ATP to
move lipids against the concentration gradient.

Note: PE is
phosphatidylethanolamine; PS
is phosphatidylserine.

15
 Membrane Rafts
Lipid distribution in a single
leaflet is not random or
uniform.
• Lipid rafts:
– contain clusters of
glycosphingolipids with
longer‐than‐usual tails
(thickened area)
– are more ordered with high
concentration of
cholesterol
– contain specific doubly or
triply acylated proteins and
GPI anchored proteins

Caveolin Forces Membrane Curvature

• Caveolin
• Integral membrane
protein with two
globular domains
• Forms dimers
• Associates with
• Caveolae cholesterol rich regions
• Unusual rafts to form caveolae
• Involved in membrane trafficking
and transduction of signals (i.e.,
insulin receptor

16
Other Modes of Membrane Curvature

• Membranes can
fuse with each
other without
exposure of lipids
to aqueous solvent.
• Fusion can be
spontaneous or
protein mediated.

Transport Across Membranes

• Cell membranes are permeable to small nonpolar
molecules that passively diffuse through the
membrane.
• Passive diffusion of polar molecules involves
desolvation and thus has a high activation barrier.
• Transport across the membrane can be facilitated by
proteins that provide an alternative diffusion path.
• Such proteins are called transporters or permeases.

17
 Transport Across Membranes
• Transport across a membrane must be
energetically favorable.
– Concentration dependence: The solute moves
toward equilibrium across the membrane.
– Electrochemical dependence: The solute moves
toward charge equilibrium across the membrane.

Types of Transport

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 Polar Solutes Need Alternative Paths
to Cross Cell Membranes

• Removal of hydration shell

which is highly endergonic

• Energy of activation (∆G‡) is

high

• Transporter protein reduces

free energy change by forming
non‐covalent interactions with
solute.

Three Classes of Transport Systems

19
 Glucose Transporter in the Membrane

α helix
Forms a pore
lined with
hydrophilic
residues for
glucose

Model for Glucose Transport

Glucose binding = T1
Conformational change = T2

20
 Bicarbonate Transporter Is an Antiporter
• CO2 is less soluble than bicarbonate
• Maintains the electrochemical potential across the membrane

Cl‐ moves into cell

to maintain
negative charge

Two Types of Active Transport

Requires energy or coupling with energetically favorable reaction.

(a) The energy released by

ATP hydrolysis drives
solute (S1) movement
against an
electrochemical
gradient
(b) A gradient of ion X (S1)
(often Na+) has been
established by primary
active transport.
Movement of X (S1)
down its
electrochemical
gradient now provides
the energy to drive
cotransport of a second
solute (S2) against its
electrochemical
gradient

21
 Peripheral Membrane Proteins
• Associate with the polar head groups of membranes
• Relatively loosely associated with membrane
– through ionic interactions with the lipids or aqueous domains
of integral membrane proteins
• Removed by disrupting ionic interactions either with
high salt or change in pH
• Purified peripheral membrane proteins are no longer
associated with any lipids.

Primary active transport: P‐type ATPase

Na/K ATPase

22
 Efficient Import of Glucose Uses Multiple
Glucose Transporters
• A Na+‐glucose symporter and a glucose uniporter
operate on opposite sides of epithelial cells to facilitate
movement of glucose from the intestine to the blood.

The Na+K+ ATPase

continues to pump Na+
outward to maintain the
Glucose is Na+ gradient that drives
cotransported with Na+ glucose uptake.
across the apical plasma
membrane into the
epithelial cell

Ion Channels Maintain Gradients

for Active Transport

• Negative AAs line the pore

• The channel consists of eight
transmembrane helices (two
from each of four identical
subunits), forming a cone.
• The cone is a selectivity filter.

23
Aquaporins Allow Rapid Water Passage
Through Membranes
The helices form a central pore, and two short helical segments
(green) contain the Asn–Pro–Ala (NPA) sequences, found in all
aquaporins, that form part of the water channel.

Chapter 11: Summary

In this chapter, we learned that:
• lipids can form micelles, bilayers, and liposomes
• membranes are composed of various lipids and proteins
• properties of the bilayer depend on the lipid composition, which
varies strongly from:
– organism to organism
– tissue to tissue
– organelle to organelle
• membrane proteins are found in three major classes and play a
variety of structural and functional roles, especially in the
transport of solutes across the membrane
• active transport of solutes across membranes requires ATP but
can be accomplished in many different ways

24
 To do…….
In this chapter, we learned that:
• Problems, pages 432‐433:
#4, 10, 11, 12, 14, 16, and 23
• Read: Boxes 11‐1 and 11‐2

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