Lipids & Membranes Lecture Note

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 & Membranes 1 Lipids anything “greasy” Lipids: Roles • Membrane structure – main structure of cell membranes • Storage of energy – reduced compounds: lots of available energy – hydrophobic nature: good packing • Signaling molecules – – – – paracrine signals (act locally) steroid hormones (act body-wide) growth factors vitamins A and D (hormone precursors) • Vitamins, Cofactors, and secondary products – – – – – Vitamins E & K: antioxidant & blood clot formation, resp. coenzyme Q: ATP synthesis in mitochondria Pigments, e.g., tomatoes, carrots, pumpkins, some birds Water repellant in feathers and hides Insulation & bouyancy control in marine mammals (blubber) 2 Lipids: Roles Functions of Membranes • Define the boundaries of the cell • Allow import and export – Selective import of nutrients (e.g. lactose) – Selective export of waste and toxins (e.g. antibiotics) • Retain metabolites and ions within the cell • Sense external signals and transmit information into the cell • Provide compartmentalization within the cell – separate energy-producing reactions from energy-consuming ones – keep proteolytic enzymes away from important cellular proteins • Produce and transmit nerve signals • Store energy as a proton gradient • Support synthesis of ATP Lipids: Roles Electron Micrograph of Biological Membranes Pancreas cell 3 Lipids: Classes Biological molecules that are characterized by low solubility in water, that is, are relatively hydrophobic. They have a high hydrocarbon content TABLE 10-2 Eight Major Categories of Biological Lipids Category Category code Examples Fatty acids ① FA Oleate, stearoyl-CoA, palmitoylcarnitine Glycerolipids ② GL Di- and triacylglycerols GP Phosphatidylcholine, phosphatidylserine, phosphatidyethanoloamine Glycerophospholipids ④ Sphingolipids SP Sphingomyelin, ganglioside GM2 ST Cholesterol, progesterone, bile acids PR Farnesol, geraniol, retinol, ubiquinone Saccharolipids SL Lipopolysaccharide Polyketides PK Tetracycline, erythromycin, aflatoxin B1 Sterol lipids ⑤ Prenol lipids Waxes ③ 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” 4 Lipids: Fatty Acids • Carboxylic acids with hydrocarbon chains containing between 4 to 36 carbons – Almost all natural fatty acids have an even number of carbons. – Most natural fatty acids are unbranched. • Biologically, most are found in ester linkages as the pKa is ~3.0, and would otherwise be very acidic. • TWO CLASSES – Saturated: no double bonds between carbons in the chain ⇌ – pKa≈3 + H+ m.p. > 37 °C – Unsaturated: ≥1 cis-double bonds between carbons in the chain m.p. < 20 °C • Monounsaturated: one double bond between carbons in the alkyl chain • Polyunsaturated: more than one double bond in the alkyl chain – never conjugated Lipids: Fatty Acids Conformation of Fatty Acids • The saturated chain tends to adopt extended conformations. • The double bonds in natural unsaturated fatty acids are in a cis configuration, which kinks the chain. C18:0 = stearate C18:1 = oleate 5 Lipids: Fatty Acids Turkey 1 18-20 12-14 Saturated FA 18-20 25-30 Unsaturated FA Lipids: Fatty Acids (D9) (D9) (D9,12) (D9,12,15) (D6,9,12) (D5,8,11,14) (D15) Need to Know: Common names, structure, symbol 6 Lipids: Fatty Acids Nomenclature • Fatty acids can be described by: – systematic name: cis-9-octadecanoic acid – common name: oleic acid 18:1w 9 – delta numbering of carbon skeleton: 18:1Δ9 • describes location of the first carbon of the alkene in relationship to the carbonyl carbon – omega numbering of carbon skeleton: 18:1ω9 • describes location of the first carbon of the alkene in relationship to the terminal methyl • Omega-3 fatty acids are essential nutrients. – Humans need them; cannot synthesize them. – They include a-linolenic acid (ALA) (18:3D 9,12,15)(18:3w 3,6,9), Eicosapentaenoic acid (EPA), and Docosahexaenoic Acid (DHA). • although DHA (22:6) and EPA (20:5) can be synthesized from ALA 22:6(D4,7,10,13,16,19) Docosahexaenoic Acid (DHA) 22:6w 3,6,9,12,15,18 20:5w 3,6,9,12,15 Lipids: Fatty Acids Solubility and Melting Point of Fatty Acids • Solubility – decreases as the chain length increases • Melting Point – decreases as the chain length decreases – decreases as the number of double bonds increases 7 Lipids: Fatty Acids Melting Point and Double Bonds • Saturated fatty acids pack in a fairly orderly way. – extensive favorable interactions What kind of interaction? • Unsaturated cis fatty acids pack less orderly due to the kink. – less-extensive favorable interactions …. van der Waals • It takes less thermal energy to disrupt disordered packing of unsaturated fatty acids. – Explains the lower melting point of unsaturated cis fatty acids. Lipids: Fatty Acids Trans Fatty Acids • Trans fatty acids form by partial hydrogenation (reduction) of unsaturated fatty acids. – done to increase shelf life or stability at high temperature of oils used in cooking (especially deep frying) – Or to convert plant oils to margarine, a solid fat (partially hydrogenated polyunsaturated oils). • A trans double bond allows a given fatty acid to adopt an extended conformation. • Trans fatty acids can pack more regularly and show higher melting points than cis forms. • Consuming trans fats increases risk of cardiovascular disease. – Avoid deep frying partially hydrogenated vegetable oils. – Current trend: reduce trans fats in foods (Wendy’s, KFC). (Eliadic acid) 8 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: Fat Triacylglycerols (Nonpolar) • The majority of fatty acids in biological systems are found in the form of triacylglycerols. – Solid ones are called fats. – Liquid ones are called oils. • The primary storage form of lipids (body fat) • Less soluble in water than fatty acids due to the esterification of the carboxylate group • Less dense than water: fats and oils float. 9 Lipids: Fat Triacylglycerols Name? 1-Myristoyl-2-stearoyl-3palmitoleoyl glycerol Tristearoyl glycerol Lipids: Fat Fats Provide Efficient Fuel Storage • The advantage of fats over polysaccharides: – Fats and oils carry more energy per carbon because they are more reduced. – Fats and oils carry less water per gram because they are nonpolar. • Glucose and glycogen are for short-term energy needs and quick delivery. • Fats are for long-term (months) energy needs, good storage, and slow delivery. • Fats can be treated with alkaline (NaOH), which will hydrolyze the ester bonds leading to glycerol and salts of the fatty acids…...soap! Process is called saponification. 10 Lipids: Fat Fats Provide Efficient Fuel Storage 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” 11 Lipids: Waxes • Waxes are esters of long-chain saturated fatty acids with and saturated or unsaturated long-chain alcohols. • Insoluble and have high melting points • Variety of functions: – waterproofing of feathers in birds – protection from evaporation in tropical plants and ivy – protection and pliability for hair and skin in vertebrates – storage of metabolic fuel in plankton – used by people in lotions, ointments, and polishes Lipids: Waxes Wax: The Material of the Honeycomb Myristic acid (C14:0) Beeswax is a mixture of a large number of lipids, including esters of triacontanol (C30:0) and cerylanol (C26:0). Ceryl alcohol (C26:0) 12 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 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 13 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 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) 14 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 15 Lipids: Membrane Lipids Examples of Glycerophospholipids H Phosphatidyl glycerol Phosphatidic = Acid Lipids: Membrane Lipids Examples of Glycerophospholipids (PA) PA PA PA + PA PA PA PA 16