Lipids and Membranes Slide 2 Functions of Lipids Energy reserves
(particularly fatty acids, lipids with long hydrocarbon chains) -
There is a large energy yield upon oxidation of these highly
reduced hydrocarbons. As lipid bilayers, main components of
biological membranes. Intra- and intercellular signaling. Slide 3
Structures of Ionized Form of Some Representative Fatty Acids Rigid
bend (~30) in hydrocarbon chain of oleic acid/oleate due to
presence of cis double bond. pK a 4.5 Slide 4 Some Fatty Acids
Saturated: no double bonds Unsaturated: one (monounsaturated) or
more (polyunsaturated) double bonds (almost always cis
configuration) 18:0 18:2c9,12 18:1c9 18:3c9,12,15 Slide 5 Some
Biologically Important Fatty Acids Most fatty acids have an even
number of carbons because they are synthesized by concatenation of
activated two-carbon units (acetyl-CoA). Slide 6 Triacylglycerols:
Fats Major energy reservoir Very efficient way to store metabolic
energy (less oxidized than carbohydrates or proteins) Slide 7 Soaps
and Detergents Sodium dodecyl sulfate Triton X-100 Hydrolysis of
fats with alkali such as NaOH or KOH yields soaps (saponification),
salts of ionized fatty acids. Synthetic detergents: Slide 8 Waxes
Formed through esterification of fatty acid and long-chain alcohol
Completely water-insoluble Water-repellent protective coating in
some animals and plants Energy storage in some microorganisms Slide
9 Glycerophospholipids (Phosphoglycerides): Main Lipid Components
of Biological Membranes Naturally occuring glycerophospholipids
have L stereochemistry. Slide 10 Glycerophospholipid Structure Kink
or bend in one fatty acyl chain in this phospholipid because of cis
double bond Hydrophilic head group Hydrophobic hydrocarbon tails =
fatty acid- derived side chains = acyl chains Slide 11 The
Hydrophilic Head Groups of Major Glycerophospholipids Slide 12
Phospholipids and Membrane Structure Bilayer Micelle Slide 13
Phospholipid Hydrolysis by Phospholipases Slide 14 Slide 15
Phospholipase A2 Bound to a Phospholipid Slide 16
Phosphatidylinositol-4,5-Bisphosphate (PIP 2 ) Hydrolysis and
Signal Transduction DG, IP 3, Ca 2+ are examples of second
messengers that transmit signals inside the cell, leading to
cellular response. IP 3 binds to Ca 2+ channels on ER membrane,
causing them to open and release of Ca 2+ into cytoplasm. Along
with Ca 2+ (released from ER as described below), DG activates
protein kinase C. Slide 17 The PIP 2 Hydrolysis Pathway Slide 18
Lipid Composition of Some Biological Membranes Slide 19
Sphingolipids: Another Major Class of Lipids Found in Biological
Membranes Ceramide Sphingosine = amino alcohol with a long
hydrocarbon chain. Ceramide = sphingosine with a fatty acid linked
by an amide bond to the amine to form an N- acyl chain.
Sphingomyelin = ceramides with a phosphocholine head group. The
myelin sheath that surrounds and electrically insulates many nerve
cell axons is rich in sphingomyelin. Black = sphingosine Black +
red = a ceramide Black + red + blue = a sphingomyelin Slide 20
Glycosphingolipids Cerebrosides = ceramides with a single sugar
residue as head group. Gangliosides = ceramides with attached
oligosaccharide as head group containing at least one sialic acid
residue. Slide 21 Gangliosides Gangliosides constitute a
significant fraction (~6%) of brain lipids. The ABO blood group
antigens are also examples of gangliosides. Slide 22 Cholesterol:
The Third Major Class of Lipid in Biological Membranes Slide 23
Cholesterol Biosynthesis Activated, five-carbon isoprene units
Cholesterol is just one of many isoprenoids (or terpenes), lipids
derived from isoprene units, which includes other steroids and
non-steroidal lipids, such as bile acids, lipid-soluble vitamins,
certain coenzymes, etc. Slide 24 Cholesterol Is the Metabolic
Precursor of Steroid Hormones Slide 25 Vitamins D Are Sterol
Derivatives Slide 26 An Example of Other Types of Lipids: The
Eiconasoids Prostaglandins Slide 27 Lipid Bilayers and Biological
Membranes Slide 28 Structure of Phospholipid Bilayer Slide 29 The
Gel-Liquid Crystalline Transition in a Lipid Bilayer and Factors
Affecting the Transition Presence of Cholesterol Moderate
concentrations of cholesterol broaden transition, making membrane
appear more fluid at lower temperatures yet less fluid at higher
temperatures. Bulky, rigid sterol ring structure of cholesterol
prevents tight packing of phospholipid acyl chains at low
temperatures. However, the rigid ring structure also reduces
mobility of phospholipid side chains at higher temperatures. Degree
of Unsaturation of Fatty Acid Side Chains Presence of phospholipids
with unsaturated fatty acyl chains reduces transition temperature,
making membrane more fluid. Bend produced by cis double bonds
prevents close packing of side chains at lower temperature. Slide
30 The Gel-Liquid Crystalline Transition in a Lipid Bilayer and
Temperature Slide 31 A Model of the Effects of Cholesterol on
Plasma Membrane Structure Slide 32 Experimental Demonstration of
Biological Membrane Fluidity Slide 33 Diffusion of Lipids in
Bilayers Translocases or flippases: protein catalysts that
facilitate transverse diffusion (flip-flop) of lipids in biological
membranes. Slide 34 Phospholipid Asymmetry in Plasma Membranes
Erythrocyte membrane Slide 35 New Lipids Inserted into Inner
Leaflet of Membrane TNBS = trinitrobenzenesulfonic acid (TNBS),
cell-impermeant reagent that reacts with phosphatidylethanolamine
Orange = newly synthesized, radioactive lipids Flip-flop rate in
biological membrane ~100,000 faster than in artificial lipid
bilayer, demonstrating efficiency of translocases. Slide 36
Structure of a Typical Cell Membrane Fluid Mosaic Model (Singer and
Nicholson, 1972). Slide 37 Protein, Lipid and Carbohydrate
Compositions of Some Membranes Slide 38 Membrane-Bound Proteins
Integral membrane proteins - span lipid bilayer; can only be
removed from membrane with strong treatments such as detergents or
organic solvents. Lipid-linked proteins - interact with membrane
via post-translationally attached lipid moeity. Peripheral membrane
proteins - weakly associated with membrane; can be dissociated with
mild treatments such as high ionic strength salt solutions or pH
changes. Slide 39 Example of a Lipid Attachment in a Lipid- Linked
Protein Other types of lipid-linked proteins: Prenylated = lipid
attachment (commonly C15 or C20) built from isoprene (C5) units
Fatty acylated = lipid attachment is fatty acid
Glycophosphosphatidylinositol (GPI) anchor of GPI-linked proteins
Slide 40 Protein Prenylation Slide 41 Model of the Structure of the
Erythrocyte Membrane Skeleton Slide 42 Major Proteins of the Human
Erythrocyte Membrane Slide 43 Glycophorin A Polypeptide Has a
Single Membrane-Spanning -Helix Intracellular domain Transmembrane
domain Extracellular domain Slide 44 Hydropathy/Hydrophobicity
Plots Bacteriorhodopsin Glycophorin A Erythrocyte glucose
transporter Slide 45 Bacteriorhodopsin: A Protein with Multiple
Membrane-Spanning -Helices Slide 46 Another Multiple-Pass
Transmembrane Protein: The Photosynthetic Reaction Center from a
Purple Bacterium Slide 47 E. coli OmpF Porin: Transmembrane Barrels
Slide 48 Vesicle Trafficking and Biosynthesis of Transmembrane and
Secreted Proteins in Eukaryotes Slide 49 Transport Across Membranes
Slide 50 Thermodynamics of Transport Free energy change (chemical
potential difference) for transporting 1 mole of a substance from
region where its concentration is C 1 (e.g., C out ) to region
where its concentration is C 2 (e.g., C in ): G = RT ln(C 2 /C 1 )
(favorable with G < 0 if C 2 < C 1 ) Transport of ions across
membrane (must consider electrical potential in addition to
concentration difference): G = RT ln(C 2 /C 1 ) + ZF (Z=charge of
ion, F=Faradays constant, =membrane electrical potential in volts)
Coupled transport (active transport): G = RT ln(C 2 /C 1 ) + G (G
of coupled process, such as ATP hydrolysis, may be negative enough
to compensate for unfavorable transport against concentration
gradient when RT ln (C 2 /C 1 ) > 0) Slide 51 Specific Transport
Processes Slide 52 Diffusional transport: movement of substance
from high to low concentration across membrane (down concentration
gradient) Non-facilitated diffusion across lipid bilayer (slow for
most biological substances) Facilitated diffusion (accelerated
diffusion by making membrane more permeable to specific transported
substance, e.g., channels and carriers) Active transport: Actively
driven (generally directly or indirectly coupled to ATP hydrolysis)
transport against concentration gradient from low to high
concentration across membrane (e.g., pumps) Modes of Transport of
Substances Across Membranes Slide 53 Types of Transport Systems
Movement of single molecule at a time Simultaneous transport of two
different molecules in same direction Simultaneous transport of two
different molecules in opposite directions Slide 54 Facilitated
Diffusion (Facilitated or Mediated Transport) Slide 55 Facilitated
and Non-Facilitated Diffusional Transport Saturable Non-saturable
Slide 56 Two Major Mechanisms for Facilitated Diffusion Slide 57
The Pore Structure of the Potassium Channel K + channel Scorpion
toxin Slide 58 Model for Glucose Transport Slide 59 The Hemolysin
Toxin from Staphylococcus aureus: A Channel-Forming Ionophore Slide
60 Gramicidin A: Another Channel-Forming Ionophore Slide 61
Valinomycin: An Antibiotic that Acts as an Ion Carrier (Carrier
Ionophore) Slide 62 ATP-Driven Active Transport Slide 63 Model for
a Subunit of the Na + /K + ATPase Slide 64 Schematic Model of the
Functional Cycle of the Na + /K + ATPase Slide 65 Slide 66 Ca +
ATPase Slide 67 Ion Gradient-Driven Active Transport Slide 68 Na +
/Glucose Cotransport (Symport) System Slide 69 Schematic Model for
the Na + /Glucose Cotransport System Slide 70 H + /Lactose
Cotransport by Lactose Permease Slide 71 Electrically Excitable
Membranes and Nerve Impulse Transmission Slide 72 Structure of a
Typical Mammalian Motor Neuron Slide 73 Use of Squid Giant Axons
for Studies of Neural Transmission Slide 74 Membrane Potential
Nernst equation (here for M Z =ion of charge Z) = RT/ZF ln([M Z ]
out /[M Z ] in ) ( =membrane potential in volts, Z=charge of ion,
F=Faradays constant) Goldman equation (takes into account multiple
ions and different permeabilities of membrane to each ion) = RT/F
ln(( + P i [M i + ] out + - P j [X j - ] in )/ ( + P i [M i + ] in
+ - P j [X j - ] out )) ( + =sum of all cations involved, - = sum
of all anions involved Ps=relative permeabilities to cations and
anions involved) Slide 75 The Action Potential Voltage-gated Na +
channel Slide 76 The Action Potential Slide 77 Transmission of the
Action Potential Slide 78 How an Axon Is Myelinated Slide 79
Techniques for the Study of Membranes Slide 80 Freeze Fracture
Slide 81 Slide 82 Preparation of Vesicles and Bilayers Slide 83
Reconstitution of the Ca 2+ Pump Slide 84 Preparation and Resealing
of Erythrocyte Ghosts Slide 85 Differential Scanning Calorimetry
Slide 86 Fluorescence Photobleaching Recovery Slide 87
