Lipids & Membranes Lecture Note 2

Lipids & Membranes A. Lipids 1. Roles 2. Classes a. b. c. d. e. Fatty Acids Fats Waxes Membrane lipids Terpenes B. Membranes 1. Introduction 2. The 4 S’s a. b. Size Solubility c. d. Shape Stability 3. Models for Membrane structure a. b. c. d. Old Model Data Fluid Mosaic Model Testing the model 4. The Red-Blood Cell Membrane 5. Membrane Asymmetry a. transverse b. c. lateral anchoring 6. Membrane Fluidity Lipids: Membrane Lipids Sphingophospholipids Sphingophospholipids Lipids: Membrane Lipids Examples of Sphingophospholipids Sphingosine (C18) Ceramide Sphingomyelin Choline Sphingomyelin §The backbone of sphingolipids is NOT glycerol. §The backbone of sphingolipids is a long-chain amino alcohol sphingosine. §A fatty acid is joined to sphingosine via an amide linkage, rather than an ester linkage as usually seen in other lipids (hence the name) = ceramide. §A polar phosphate group is connected to ceramide by a phospho-ester linkage = sphingomyelin. §A polar alcohol is connected by another phosphoester linkage = Choline sphingomyelin or Ethanolamine sphingomyelin •Choline Sphingomyelin = Ceramide (sphingosine + amide-linked fatty acid) + phosphocholine attached to the C1-alcohol of sphingosine •Sphingomyelin is abundant in myelin sheath that surrounds some nerve cells in animals. Lipids: Membrane Lipids Sphingophospholipids Sphingomyelin Choline Ethanolamine Sphingomyelin – – – Phosphoethanolamine H3 Lipids: Membrane Lipids Sphingomyelin is Structurally Similar to Phosphatidylcholine Lipids: Membrane Lipids Sphingoglycolipids Sphingoglycolipids outer face of plasma membranes. Lipids: Membrane Lipids Sphingoglycolipids Ceramide Cerebroside Globoside Ganglioside Gangling = tall, thin, and awkward Lipids: Membrane Lipids Sphingoglycolipids Lipids: Classes Biological molecules that are characterized by low solubility in water, that is, are relatively hydrophobic. Classes of Lipids They have a high hydrocarbon content 1. Fatty acids 2. Fats (triglycerides) 3. Waxes 4. Membrane Lipids 5. Isoprenes 2 & 3 are sometimes classified together as ”simple lipids” Lipids: Membrane Lipids Cholesterol & Terpenes (Isoprenes) isoprene 2 x isoprene = terpene C5 Lipids: Membrane Lipids Cholesterol & Terpenes (Isoprenes) Lipids Can Provide Pigment Lipids: Membrane Lipids Cholesterol & Terpenes (Isoprenes) • Cholesterol – – – – Tri-terpene steroid nucleus: four fused rings (lanosterol) hydroxyl group (polar head) in the A-ring Need to Know: Structure, numbering various nonpolar side chains • The tetracycle structure of Cholesterol is almost planar. Lipids: Membrane Lipids Cholesterol & Terpenes (Isoprenes) • Cholesterol and related sterols are present in the membranes of most eukaryotic cells. – modulate fluidity and permeability – thicken the plasma membrane – no sterols in most bacteria • Mammals obtain cholesterol from food or synthesize it de novo in the liver. • Cholesterol, bound to proteins, is transported to tissues via blood vessels. – When in excess, cholesterol in low-density lipoproteins (LDLs) tends to deposit and clog arteries. • Bile acids and many hormones are derivatives of cholesterol. 12 A Metabolic Hormone (made by adrenal gland) 11 17 7 Sex Hormones (made by the gonads) A Bile Acid (made by liver) -19 Lipids: Membrane Lipids V. radiata Plasma Membrane* 0 32 – 39 4 2 2 – – *This is the mung bean and the PM contains a large fraction of phosphatidic acid (21%). From Yoshida et al. (1986) Plant Physiol 82:807 Lipids: Membrane Lipids *This is the mung bean and the PM contains a large fraction of phosphatidic acid (21%). From Yoshida et al. (1986) Plant Physiol 82:807 Lipids: Membranes Introduction The 4 S’s Size Solubility Shape Stability Models for Membrane structure Old Model Data Fluid Mosaic Model Testing the model The Red-Blood Cell Membrane Membrane Asymmetry Lipids transverse lateral Protein anchoring glycoproteins Membrane Fluidity Lipids: Membranes • 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). • Membranes are complex lipid-based structures that form stable, dynamic, pliable “sheets”/barriers • Membranes are composed of a variety of lipids and proteins Lipids: Membrane Proteins TABLE 11-1 Major Components of Plasma Membranes in Various Organisms Components (% by weight) Human myelin sheath Protein Phosphlipid Sterol Sterol type Other lipids 30 30 19 Cholesterol Galactolipids, plasmalogens Mouse liver 45 27 25 Cholesterol — Maize leaf 47 26 7 Sitosterol Galactolipids Yeast 52 7 4 Ergosterol Triacylglycerols, steryl esters Paramecium (ciliated protist) 56 40 4 Stigmasterol — E. coli 75 25 0 — — Note: Values do not add up to 100% in every case because there are components other than protein, phospholipids, and sterol; plants, for example, have high glycolipid content. Membrane Composition Is Highly Variable in Different Organisms… and different organelles Lipids: Membranes The 4 S’s Size Shape Solubility Stability Lipids: Membranes 8Å Size Polar Head group Phospholipids: Non-polar tails Membranes: 40-60 Å Shape Polar Head group Non-polar tails It has a “trilaminar” structure as seen in the EM What are the consequences of this shape? Lipids: Membranes Shape • Two major structures are observed: –Bilayers/vesicles –micelles • Structures formed depend on: – type of lipid What is this concentration dependence? – Concentration • Both form spontaneously in aqueous solution and are stabilized by noncovalent forces, especially hydrophobic effect due to amphipathic molecules: large polar head & tail –Examples that form micelles: fatty acids, sodium dodecyl sulfate –Examples that form bilayers: phospholipids, glycolipids • Micelles are composed of a few dozen to a few thousand lipid molecules. Lipids: Membranes The 4 S’s Size Shape Solubility Stability Lipids: Membranes Solubility • The first molecules, at low concentration, go to the air/liquid Detergent interface and form a monolayer. • Once that is crowded, they “dissolve” in the water • Once the concentration is sufficient to form aggregates, micelles or vesicles form. • Depending on the lipid, this concentration is called the “Critical Phospholipid Micellular Concentration” (CMC). Lipids: Membranes Solubility: Membrane Bilayer • Consists of two leaflets (e.g., layers) of lipid monolayers – Forms when lipids with polar head groups and more than one lipid tail are in aqueous solution • phospholipids • sphingoglycolipids – Hydrophilic head groups interact with water on both sides of the bilayer. – Hydrophobic fatty acid tails are packed inside. Vesicle (Liposome) Originally called Bangosomes after Sir Alex Bangham Lipids: Membranes The 4 S’s Size Shape Solubility Stability Lipids: Membranes Stability • 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. • Permeable to hydrophobic molecules (lipids, e.g., steroids) and water, but not permeable to large polar solutes and ions • Dynamic and flexible structures Lipids: Membranes Stability: Biochemical • Most cells continually degrade and replace their membrane lipids. • Phospholipids are degraded by phospholipases A−D. N. naja C. adamanteus Lipids: Membranes Introduction The 4 S’s Size Solubility Shape Stability Models for Membrane structure Old Model Data Fluid Mosaic Model Testing the model The Red-Blood Cell Membrane Membrane Asymmetry Lipids transverse lateral Protein anchoring glycoproteins Membrane Fluidity Lipids: Membranes Models for Membrane Structure OLD MODEL (ca. 1940-1970) Sandwich model proposed by DanielliDavson. Based on the structures in the EM Bilayer Membrane proteins (mostly have b-structure) Scientifically, this is a good MODEL because it is clearly TESTABLE! This model makes several testable predictions: 1) Protein-lipid interactions should be mostly electrostatic; proteins should have lots of charged groups. 2) Should be able to “wash” nearly all membrane proteins off the membranes with high salt. 3) Isolated membrane proteins should show lots of b-structure 4) Importantly, NO PROTEINS ON THE INSIDE