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Chapter 9 - Lipids and
Membranes
• Lipids are essential components of all living
organisms
• Lipids are water insoluble organic compounds
• They are hydrophobic (nonpolar) or
amphipathic (containing both nonpolar and
polar regions)
Structural and Functional
Diversity of Lipids
• Fatty acids - R-COOH (R=hydrocarbon chain)
are components of triacylglycerols,
glycerophospholipids, sphingolipids
• Phospholipids - contain phosphate moieties
• Glycosphingolipids - contain both sphingosine
and carbohydrate groups
• Isoprenoids - (related to the 5 carbon isoprene)
include steroids, lipid vitamins and terpenes
Structural relationships
of major lipid classes
Fatty Acids
• Fatty acids (FA) differ from one another in:
(1) Length of the hydrocarbon tails
(2) Degree of unsaturation (double bond)
(3) Position of the double bonds in the chain
Nomenclature of fatty acids
• Most fatty acids have 12 to 20 carbons
• Most chains have an even number of carbons
(synthesized from two-carbon units)
• IUPAC nomenclature: carboxyl carbon is C-1
• Common nomenclature: a,b,g,d,e etc. from C-1
• Carbon farthest from carboxyl is w
Structure and nomenclature of fatty acids
• Saturated FA - no C-C double bonds
• Unsaturated FA - at least one C-C double bond
• Monounsaturated FA - only one C-C double
bond
• Polyunsaturated FA - two or more C-C double
bonds
Double bonds in fatty acids
• Double bonds are generally cis
• Position of double bonds indicated by Dn, where
n indicates lower numbered carbon of each pair
• Shorthand notation example: 20:4D5,8,11,14
(total # carbons : # double bonds, D double bond positions)
Structure and nomenclature
of fatty acids
Fatty acids are stored as triglycerols
(triglycerides)
Glycerophospholipids
• The most abundant lipids in membranes
• Possess a glycerol backbone
• A phosphate is esterified to both glycerol and
another compound bearing an -OH group
• Phosphatidates are glycerophospholipids with
two fatty acid groups esterified to C-1 and C-2
of glycerol 3-phosphate
(a) Glycerol 3-P and (b) phosphatidate
O
O P O
O
(a)
H2 C
CH
CH2
O
O P O
O
H2 C
OH OH
O
(b)
CH2
CH
O
O
O
Glycerol 3-phosphate
phosphatidate
(R1) (R2)
Structures of glycerophospholipids
(a) Phosphatidyl ethanolamine
(b) Phosphatidyl serine
(c) Phosphatidylcholine
NH3
CH2
NH3
CH COO
CH2
O
O P O
O
H2 C
O
CH2
CH
CH2
O
O P O
O
H2 C
O
O
O
R1 R2
phosphatidylethanolamine
CH3
H3C CH3
N
CH2
O
CH2
CH
CH2
O
O P O
O
H2 C
O
O
O
R1 R2
phosphatidylserine
O
CH2
CH
O
O
O
R1 R2
phosphatidylcholine
Phospholipases hydrolyze phospholipids
Structure of an
ethanolamine
plasmalogen
• Plasmalogens - C-1
hydrocarbon substituent
attached by a vinyl ether
linkage (not ester linkage)
Sphingolipids
• Sphingolipids - sphingosine (trans-4-sphingenine)
is the backbone (abundant in central nervous
system tissues )
• Ceramides - fatty acyl group linked to C-2 of
sphingosine by an amide bond
• Sphingomyelins - phosphocholine attached to C-1
of ceramide
• Cerebrosides - glycosphingolipids with one
monosaccharide residue attached via a
glycosidic linkage to C-1 of ceramide
• Galactosylcerebrosides (galactosylceramides)
- a single b-D-galactose as a polar head group
• Gangliosides - contain oligosaccharide chains
with N-acetyl-neuraminic acid (NeuNAc)
attached to a ceramide
• Structure of a
galactocerebroside
Ganglioside GM2
(NeuNAc in blue)
Steroids
• Classified as isoprenoids - related to 5carbon isoprene (found in membranes of
eukaryotes)
• Steroids contain four fused ring systems: 3six carbon rings (A,B,C) and a 5-carbon D
ring
• Ring system is nearly planar
• Substituents point either down (a) or up (b)
Cholesteryl ester
Other Biologically Important Lipids
• Waxes are nonpolar esters of long-chain fatty
acids and long chain monohydroxylic alcohols
• Waxes are very water insoluble and high melting
• They are widely distributed in nature as
protective waterproof coatings on leaves, fruits,
animal skin, fur, feathers and exoskeletons
Myricyl palmitate, a wax
Eicosanoids
• Eicosanoids are oxygenated derivatives of C20
polyunsaturated fatty acids (e.g. arachidonic
acid)
• Prostaglandins - eicosanoids having a
cyclopentane ring
• Aspirin alleviates pain, fever, and inflammation
by inhibiting the synthesis of prostaglandins
Prostaglandins
Prostaglandins
are involved in many
biological processes.
Are biosynthesized from linoleic acid (C18)
via arachidonic acid (C20).
CO2H
cyclooxygenase
aspirin inhibits enzyme
O
Prostaglandins
OH
COOH
HO
OH
Prostaglandin E2
COOH
HO
OH
Prostaglandin F 1
(Chimes?)
Examples: PGE1 and PGF1a
O
O
HO
PGE1
OH
PGF1a
OH
O
HO
HO
OH
OH
Aspirin Inhibits the Synthesis of
Prostaglandins
Biological Membranes Are Composed
of Lipid Bilayers and Proteins
• Biological membranes define the external
boundaries of cells and separate cellular
compartments
• A biological membrane consists of proteins
embedded in or associated with a lipid bilayer
Several important functions of
membranes
• Some membranes contain protein pumps for
ions or small molecules
• Some membranes generate proton gradients for
ATP production
• Membrane receptors respond to extracellular
signals and communicate them to the cell interior
Lipid Bilayers
• Lipid bilayers are the structural basis for all
biological membranes
• Noncovalent interactions among lipid molecules
make them flexible and self-sealing
• Polar head groups contact aqueous medium
• Nonpolar tails point toward the interior
Membrane lipid and bilayer
Fluid Mosaic Model of Biological Membranes
• Fluid mosaic model - membrane proteins and
lipids can rapidly diffuse laterally or rotate within
the bilayer (proteins “float” in a lipid-bilayer sea)
• Membranes: ~25-50% lipid and 50-75% proteins
• Lipids include phospholipids, glycosphingolipids,
cholesterol (in some eukaryotes)
• Compositions of biological membranes vary
considerably among species and cell types
Structure of a typical eukaryotic
plasma membrane
Lipid Bilayers and Membranes
Are Dynamic Structures
(a)Lateral diffusion is very rapid
(b) Transverse diffusion (flip-flop) is very slow
Phase transition of a lipid bilayer
• Fluid properties of bilayers depend upon
the flexibility of their fatty acid chains
Three Classes of Membrane Proteins
(1) Integral membrane proteins (or intrinsic
proteins or trans-membrane proteins)
(2) Peripheral membrane proteins
(3) Lipid-anchored membrane proteins
Lipid-anchored membrane proteins
Membrane Transport
• Three types of integral membrane protein
transport:
(1) Channels and pores
(2) Passive transporters
(3) Active transporters
Table 9.3 Characteristics of
membrane transport
A. Pores and Channels
• Pores and channels are transmembrane
proteins with a central passage for ions and
small molecules
• Solutes of appropriate size, charge, and
molecular structure can diffuse down a
concentration gradient
• Process requires no energy
• Rate may approach diffusion-controlled limit
Membrane transport
through a pore or channel
• Central passage
allows molecules and
ions of certain size,
charge and geometry
to transverse the
membrane
B. Passive Transport
• Passive transport (facilitated diffusion) does not
require an energy source
• Protein binds solutes and transports them down
a concentration gradient
Types of passive transport
systems

Uniport - transporter carries only a single type of
solute

Some transporters carry out cotransport of two
solutes, either in the same direction (symport) or in
opposite directions (antiport)
Kinetics of passive transport
• Initial rate of
transport
increases until a
maximum is
reached (site is
saturated)
The erythrocyte membrane contains channels that
function to exchange anions, such as chloride (Cl-)
and bicarbonate (HCO3-), across the membrane
bilayer. From the following data, describe the
effect that exogenous sulfate (SO4-) has on (Cl-)
influx in erythroyctes.
C. Active Transport
• Transport requires energy to move a solute up
its concentration gradient
• Transport of charged molecules or ions may
result in a charge gradient across the
membrane
Types of active transport

Primary active transport is powered by a
direct source of energy as ATP, light or
electron transport

Secondary active transport is driven by an
ion concentration gradient
• Primary active transport
protein function
• Protein binds specific
substrate, conformational
change allows molecule or
ion to be released on the
other side of the membrane
Secondary active transport in E. coli
• Oxidation of Sred
generates a
transmembrane
proton gradient
• Movement of H+
down its gradient
drives lactose
transport (lactose
permease)
Secondary active transport
in animals: Na+-K+ ATPase
• Na+ gradient (Na+-K+ATPase) drives glucose transport
VALINOMYCIN
Transduction of Extracellular Signals
• Specific receptors in plasma membranes
respond to external chemicals (ligands) that
cannot cross the membrane: hormones,
neurotransmitters, growth factors
• Signal is passed through membrane protein
transducer to a membrane-bound effector
enzyme
• Effector enzyme generates a second
messenger which diffuses to intracellular target
General mechanism of signal transduction
across a membrane
G Proteins are Signal
Transducers
• Many hormone receptors rely on guanine
nucleotide-binding proteins (G proteins) as
transducers
• G proteins have GTPase activity: they slowly
hydrolyze the bound GTP to GDP and Pi
• Two interconvertible forms of G proteins: an
inactive GDP-bound form and an active GTPbound form
Composition of G-proteins
• G proteins consist of a,b and g subunits
• The Ga-GTP complex interacts with the
effector enzyme
• Hydrolysis of GTP by the Ga-GTP complex
deactivates the G protein and permits
assembly of the inactive Gabg complex
Hydrolysis of GTP to GDP and Pi
G-protein cycle
• G proteins are
activated by binding
to a receptor-ligand
complex
• G-proteins are
inactivated slowly by
their own GTPase
activity
B. The Adenylyl Cyclase
Signaling Pathway
• cAMP and cGMP are second messengers
• They transmit information from extracellular
hormones to intracellular enzymes
• Many hormones that regulate intracellular
metabolism exert effects on target cells by
activating cAMP pathway
cAMP response to hormones
• Hormones active the G protein Gs
• Gs activates adenylyl cyclase enzyme to
produce cAMP
• cAMP activates protein kinases to
phosphorylate cellular enzymes and
affect metabolic pathway processes
Production,inactivation of cAMP
• Activation of
protein kinase A
by cAMP
Caffeine, theophylline inhibit
cAMP phosphodiesterase
• Inhibition of cAMP phosphodiesterases
prolongs the effects of cAMP
• This increases the intensity and duration of
stimulatory hormones
• Summary of
the adenyl
cyclase
signaling
pathway
The Inositol-Phospholipid
Signaling Pathway
• A major signal-transduction pathway for some
hormones, growth factors (2 second messengers)
• Diacylglycerol and IP3 (inositol 1,4,5 triphosphate)
are produced from the membrane phospholipid
PIP2 (phosphatidylinositol 4,5-bisphosphate)
• IP3 activates a calcium channel
• Diacylglycerol activates protein kinase C
Phosphatidylinositol 4,5-bisphosphate (PIP2)
produces IP3 and diacylglycerol
• Inositolphospholipid
signaling
pathway
D. Receptor Tyrosine Kinases
(TK)
• Many growth factors operate by a signaling
pathway involving a tyrosine kinase
• TK is a multifunctional transmembrane protein
containing a receptor, a transducer, and an
effector
• Binding of a ligand to the extracellular receptor
domain activates tyrosine kinase (intracellular)
• Activation of receptor
tyrosine kinases by
ligand-induced
dimerization
• Phosphorylated dimer
phosphorylates
cellular target proteins
• Each domain
catalyzes
phosphorylation
of its partner
Insulin receptor and tyrosine kinase activity
• Insulin binds to 2
extracellular a-chains
• Transmembrane b-chains
then autophosphorylate
• Tyrosine kinase domains
then phosphorylate insulinreceptor substrates (IRSs)
(which are proteins)
Insulin-stimulated formation of PIP3