Lipids Membranes Biological Molecules That are Characterized by Low Solubility

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” 1 Lipids: Membrane Lipids Classification of Membrane Lipids Two major categories based on the structure and function: 1. Lipids that contain phosphate 2. Lipids that do not contain phosphate – each can be further separated into: • Glycerol-based and sphingosine-based (animals) Cholesterol Sphingophospholipids Sphingolipids Sphingoglycolipids All these structures are related to those of FAT… Lipids: Membrane Lipids Membrane Lipids Glycerolphospholipids Phosphatidic Acid (more precisely, 1,2-distearoyl-phosphatidic acid) 2 Lipids: Membrane Lipids General Structure of Glycerophospholipids 1-Palmitoyl-2-linoleoylphosphatidyl-X(name of alcohol) • Primary constituents of cell membranes • The phosphate group is negatively charged at physiological pH. • Two fatty acids form ester linkages with the first and second hydroxyl groups of Lglycerol-3-phosphate. Unsaturated fatty acids are commonly found connected to C2 of glycerol-3phosphate. The highly polar phosphate group may be further esterified by an alcohol; such substituent groups are called the head groups (another phospho-diester linkage). • • What are these “head groups?” Lipids: Membrane Lipids Depictions of Glycerophospholipids O P O– 1-Stearoyl-2-linoleoyl-3-phosphatidyl-choline Polar Head group Non-polar tails 3 Lipids: Membrane Lipids Examples of Glycerophospholipids (PE) (PS) (PC) H Phosphatidyl glycerol (PG) (PI) Phosphatidic = Acid (DPG) Lipids: Membrane Lipids Examples of Glycerophospholipids Abbrev. (PA) PA PA PA PE PA + PC PS PA PA PG PA PI PA DPG 4 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. 5 Lipids: Membrane Lipids Sphingophospholipids Sphingomyelin Choline Ethanolamine Sphingomyelin – – – Phosphoethanolamine H3 Lipids: Membrane Lipids Sphingomyelin is Structurally Similar to Phosphatidylcholine 6 Lipids: Membrane Lipids Sphingoglycolipids Sphingoglycolipids outer face of plasma membranes. Lipids: Membrane Lipids Sphingoglycolipids Ceramide Cerebroside Globoside Ganglioside Gangling = tall, thin, and awkward 7 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” 8 Lipids: Membrane Lipids Cholesterol & Terpenes (Isoprenes) isoprene 2 x isoprene = terpene C5 Lipids: Membrane Lipids Cholesterol & Terpenes (Isoprenes) Lipids Can Provide Pigment 9 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. A Metabolic Hormone 12 (made by adrenal gland) 11 17 7 Sex Hormones (made by the gonads) A Bile Acid (made by liver) -19 10 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: 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 11 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 12 Lipids: Membrane Proteins TABLE 11-1 Major Components of Plasma Membranes in Various Organisms Components (% by weight) Protein Phosphlipid Sterol Sterol type Other lipids Human myelin sheath 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 13 Lipids: Membranes 8Å Size Polar Head group Phospholipids: 2030 Å 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. 14 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). 15 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 Vesicle (Liposome) Originally called Bangosomes after Sir Alex Bangham – Hydrophilic head groups interact with water on both sides of the bilayer. – Hydrophobic fatty acid tails are packed inside. Lipids: Membranes The 4 S’s Size Shape Solubility Stability 16 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 17