Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Lipids and Membranes 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. Structures of Ionized Form of Some Representative Fatty Acids pKa ≈ 4.5 Rigid bend (~30º) in hydrocarbon chain of oleic acid/oleate due to presence of cis double bond. Some Fatty Acids •Saturated: no double bonds •Unsaturated: one (monounsaturated) or more (polyunsaturated) double bonds (almost always cis configuration) 18:2c∆9,12 18:0 18:1c∆9 18:3c∆9,12,15 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). Triacylglycerols: Fats OH HO OH Glycerol •Major energy reservoir •Very efficient way to store metabolic energy (less oxidized than carbohydrates or proteins) Soaps and Detergents •Hydrolysis of fats with alkali such as NaOH or KOH yields soaps (saponification), salts of ionized fatty acids. •Synthetic detergents: Sodium dodecyl sulfate Triton X-100 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 Glycerophospholipids (Phosphoglycerides): Main Lipid Components of Biological Membranes Naturally occuring glycerophospholipids have L stereochemistry. Glycerophospholipid Structure Hydrophilic “head” group Kink or bend in one fatty acyl chain in this phospholipid because of cis double bond Hydrophobic hydrocarbon “tails” = fatty acidderived side chains = acyl chains The Hydrophilic Head Groups of Major Glycerophospholipids Phospholipids and Membrane Structure Micelle Bilayer Phospholipid Hydrolysis by Phospholipases Phospholipase A2 Bound to a Phospholipid Phosphatidylinositol-4,5-Bisphosphate (PIP2) Hydrolysis and Signal Transduction Along with Ca2+ (released from ER as described below), DG activates protein kinase C. IP3 binds to Ca2+ channels on ER membrane, causing them to open and release of Ca2+ into cytoplasm. DG, IP3, Ca2+ are examples of “second messengers” that transmit signals inside the cell, leading to cellular response. The PIP2 Hydrolysis Pathway Lipid Composition of Some Biological Membranes Sphingolipids: Another Major Class of Lipids Found in Biological Membranes Black = sphingosine Black + red = a ceramide Black + red + blue = a sphingomyelin 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 Nacyl chain. Sphingomyelin = ceramides with a phosphocholine head group. The myelin sheath that surrounds and electrically insulates many nerve cell axons is rich in sphingomyelin. 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. Gangliosides Gangliosides constitute a significant fraction (~6%) of brain lipids. The ABO blood group antigens are also examples of gangliosides. Cholesterol: The Third Major Class of Lipid in Biological Membranes 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. Cholesterol Is the Metabolic Precursor of Steroid Hormones Vitamins D Are Sterol Derivatives HO HO Vitamin D3 Vitamin D2 An Example of Other Types of Lipids: The Eiconasoids Prostaglandins Lipid Bilayers and Biological Membranes Structure of Phospholipid Bilayer The Gel-Liquid Crystalline Transition in a Lipid Bilayer and Factors Affecting the Transition 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. 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. The Gel-Liquid Crystalline Transition in a Lipid Bilayer and Temperature A Model of the Effects of Cholesterol on Plasma Membrane Structure Experimental Demonstration of Biological Membrane Fluidity Diffusion of Lipids in Bilayers Translocases or flippases: protein catalysts that facilitate transverse diffusion (flip-flop) of lipids in biological membranes. Phospholipid Asymmetry in Plasma Membranes Erythrocyte membrane New Lipids Inserted into Inner Leaflet of Membrane Orange = newly synthesized, radioactive lipids TNBS = trinitrobenzenesulfonic acid (TNBS), cell-impermeant reagent that reacts with phosphatidylethanolamine Flip-flop rate in biological membrane ~100,000 faster than in artificial lipid bilayer, demonstrating efficiency of translocases. Structure of a Typical Cell Membrane Fluid Mosaic Model (Singer and Nicholson, 1972). Protein, Lipid and Carbohydrate Compositions of Some Membranes 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. Example of a Lipid Attachment in a LipidLinked Protein Glycophosphosphatidylinositol (GPI) anchor of GPI-linked proteins 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 Protein Prenylation Model of the Structure of the Erythrocyte Membrane Skeleton Major Proteins of the Human Erythrocyte Membrane Glycophorin A Polypeptide Has a Single Membrane-Spanning a-Helix Extracellular domain Intracellular domain Transmembrane domain Hydropathy/Hydrophobicity Plots Glycophorin A Erythrocyte glucose transporter Bacteriorhodopsin Bacteriorhodopsin: A Protein with Multiple Membrane-Spanning a-Helices Another Multiple-Pass Transmembrane Protein: The Photosynthetic Reaction Center from a Purple Bacterium E. coli OmpF Porin: Transmembrane b Barrels Vesicle Trafficking and Biosynthesis of Transmembrane and Secreted Proteins in Eukaryotes Transport Across Membranes Thermodynamics of Transport • Free energy change (chemical potential difference) for transporting 1 mole of a substance from region where its concentration is C1 (e.g., Cout) to region where its concentration is C2 (e.g., Cin): ∆G = RT ln(C2/C1) (favorable with ∆G < 0 if C2 < C1) • Transport of ions across membrane (must consider electrical potential in addition to concentration difference): ∆G = RT ln(C2/C1) + ZF ∆ (Z=charge of ion, F=Faraday’s constant, ∆=membrane electrical potential in volts) • Coupled transport (active transport): ∆G = RT ln(C2/C1) + ∆G´ (∆G´ of coupled process, such as ATP hydrolysis, may be negative enough to compensate for unfavorable transport concentration gradient when RT ln (C2/C1) > 0) against Specific Transport Processes Modes of Transport of Substances Across Membranes • 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) 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 Facilitated Diffusion (Facilitated or Mediated Transport) Facilitated and Non-Facilitated Diffusional Transport Saturable Non-saturable Two Major Mechanisms for Facilitated Diffusion The Pore Structure of the Potassium Channel Scorpion toxin K+ channel Model for Glucose Transport The Hemolysin Toxin from Staphylococcus aureus: A Channel-Forming Ionophore Gramicidin A: Another Channel-Forming Ionophore Valinomycin: An Antibiotic that Acts as an Ion Carrier (Carrier Ionophore) ATP-Driven Active Transport Model for a Subunit of the Na+/K+ ATPase Schematic Model of the Functional Cycle of the Na+/K+ ATPase Ca+ ATPase Ion Gradient-Driven Active Transport Na+/Glucose Cotransport (Symport) System Schematic Model for the Na+/Glucose Cotransport System H+/Lactose Cotransport by Lactose Permease Electrically Excitable Membranes and Nerve Impulse Transmission Structure of a Typical Mammalian Motor Neuron Use of Squid Giant Axons for Studies of Neural Transmission Membrane Potential •Nernst equation (here for MZ=ion of charge Z) ∆ = RT/ZF ln([MZ]out/[MZ]in) (∆=membrane potential in volts, Z=charge of ion, F=Faraday’s constant) •Goldman equation (takes into account multiple ions and different permeabilities of membrane to each ion) ∆ = RT/F ln((+ Pi[Mi+]out + - Pj[Xj-]in)/ (+ Pi[Mi+]in + - Pj[Xj-]out)) (+=sum of all cations involved, -= sum of all anions involved P’s=relative permeabilities to cations and anions involved) The Action Potential Voltage-gated Na+ channel The Action Potential Transmission of the Action Potential How an Axon Is Myelinated Techniques for the Study of Membranes Freeze Fracture Freeze Fracture Preparation of Vesicles and Bilayers Reconstitution of the Ca2+ Pump Preparation and Resealing of Erythrocyte Ghosts Differential Scanning Calorimetry Fluorescence Photobleaching Recovery