Lecture 5 Lipids PDF

Lecture 5 LIPIDS TOPIC OUTLINE Functions of Lipids Physical Properties of Fatty Acids Structure and Classification of Lipids Biological Membranes Membrane Proteins The Function of Membranes The Lipid-Soluble Vitamins LIPIDS a heterogeneous class of naturally occurring organic...

Lecture 5 LIPIDS TOPIC OUTLINE Functions of Lipids Physical Properties of Fatty Acids Structure and Classification of Lipids Biological Membranes Membrane Proteins The Function of Membranes The Lipid-Soluble Vitamins LIPIDS a heterogeneous class of naturally occurring organic compounds with varying chemical composition and classified together based on their solubility with nonpolar solvents insoluble in water due to the long chains of hydrocarbon (C-H) bonds Amphipathic in nature LIPIDS Interaction of biochemical compounds with water When placed in water, simple lipids form structures like micelles, arranging themselves spherically in an aqueous solution. Functions of Lipids Energy Source Protection and & Storage Insulation Cell Membrane Vitamins and Structural Vitamin Component Absorption Chemical Messengers (Hormones)  Types of Lipids Fatty Acids Saturated Unsaturated Glycerides glycerol-containing lipids Nonglyceride lipids Sphingolipids Steroids Waxes Complex lipids (lipoproteins) Types of Lipids Structure of Lipids Lipids exhibit structural diversity Some are esters, some are amides, and some are alcohols (acyclic and cyclic) and some are polycyclic.  Fatty Acids an unbranched-chain carboxylic acid, most commonly of 12 - 20 carbons, derived from hydrolysis of animal fats, vegetable oils, or phosphodiacylglycerols of biological membranes Even # of Carbon atoms: (a) Long-chain fatty acids: C12 - C26 (b) Medium-chain fatty acids: C6 - C11 (c) Short-chain fatty acids: C4 - C5 Two Types of Fatty Acids: 1. Saturated - all C-C bonds are single bonds 2. Unsaturated – (a) monounsaturated: one C=C bond (b) polyunsaturated: 2 or more C=C bonds present - up to six double bonds are present in fatty acids nonpolar polar  Fatty Acids a. saturated b. monounsaturated c. polyunsaturated Fatty Acids Examples of Common Fatty Acids The common fatty acids found in biological systems are shown in Table 8.1 Structure of Fatty Acids  Examples of Fatty Acids Omega Fatty Acids Nutritionally important Omega-3 and Omega-6 fatty acids Linolenic acid – Omega-3 Linoleic acid – Omega-6 Linoleic Acid Deficiency: - Skin redness - becomes irritated - Infections and dehydration - Liver abnormalities - Children need it the most  Essential Fatty Acids Alpha Linolenic Acid (ALA) - found in plants (flaxseed, walnuts, canola and soybean DHA and EPA - marine sources - produced by microalgae (anchovies, mackerel, salmon and sardines)  Essential Fatty Acids Linoleic Acid - found in safflower, corn and soybean oils Arachidonic Acid - fish, meat and eggs - precursor of eicosanoids  Properties of Fatty Acids Water solubility: Short- chain fatty acids are sparingly soluble whereas long-chain fatty acids are insoluble Melting Point Depends Upon: - length of the carbon chain - degree of unsaturation (number of double bonds in a molecule)  Properties of Fatty Acids Space-Filling Molecules - the number of bends in a fatty acid chain increases as the number of double bonds increases - Less packing occurs - The melting point is lower - Tend to be liquids at room temperature Classification of Lipids  BIOLOGICAL WAXES A mixture of esters of long-chain carboxylic acids and alcohols Found as protective coatings for plants and animals Commonly used in pharmaceuticals and cosmetics Carnauba Wax  Glycerides Esterification of Monoglyceride Lipid esters of glycerol and fatty acids (monoglycerides, diglycerides, and triglycerides) Two Classes: neutral glycerides Monoglyceride and (nonionic and Diglyceride are nonpolar) widely used as Phosphoglycerides emulsifying agents (amphipathic) Triglycerides (Triacylglycerols) Esters of 1 molecule of glycerol with three fatty acids (TAGs) called neutral fats and serve as energy storage in the fat cells of adipose tissue. FATS (solid) OILS (liquid) derived from animals (beef, pork, & derived from plants and marine chicken) animals (essential oils and fish oil) mixture of high percentage of long Mixture of a high degree of chains saturated FA and less degree of unsaturated fatty acids and less of unsaturation saturated FA Triglycerides (Triacylglycerols)  Reactions of Fatty Acids and Glycerides Esterification Fatty acids react with long chain alcohols to produce water and esters (biological waxes)  Reactions of Fatty Acids and Glycerides Esterification 3 molecules of fatty acids react with glycerol to produce water and triglyceride  Reactions of Fatty Acids and Glycerides Hydrogenation an addition reaction when unsaturated fatty acids are converted to saturated fatty acids commonly used in the food industry Reactions of Fatty Acids and Glycerides Hydrogenation  Reactions of Fatty Acids and Glycerides Acid Hydrolysis Waxes or triglycerides may be hydrolyzed in the presence of acid or biological enzymes to form alcohol and fatty acids  Reactions of Fatty Acids and Glycerides Saponification (Base Hydrolysis) natural soaps (fatty acid salts) are prepared by boiling triglycerides (animal fats or vegetable oils) with NaOH or KOH in a reaction Reactions of FattyAcids and Glycerides Saponification (Base Hydrolysis)  Phospholipids Phosphate ester lipids derived from phosphoric acid polar head (the phosphoryl group) and a nonpolar tail (the alkyl chain of the fatty acid) Phospholipids dominate up to 80% of the mass of a cell membrane. Types: Phosphoglycerides (Phosphoacylglycerides) Sphingolipids (Sphingomyelin) Phospholipids Unlike the soaps, these molecules are highly amphipathic, and when mixed with water spontaneously form membranes that are described as lipid bilayers. Soaps form Phospholipids form Micelles Lipid Bilayers Phospholipids Phosphoglycerides Also known as Phosphoacylglycerols or Glycerophospholipids Glycerol is esterified to phosphoric acid Phosphatidic acid is esterified to 2 fatty acids -OH group from Phosphatidic acid is esterified to an amino alcohols (R group) Most abundant type of phospholipids in the cell membrane Phosphatidate is the simplest Phosphoglycerides The classification of phosphatidyl ester depends on the nature of the second alcohol esterified to phosphoric acid Phosphoglycerides Phosphatidylcholine known as Lecithin major constituent of cell membrane and pulmonary surfactant micelle-forming agents (emulsifying agent) Phosphoglycerides Phosphatidylethanolamine known as Cephalins Found in brain tissue and nerves Responsible for blood coagulation Phosphoglycerides Phosphatidylserine isolated from brain lipids and considered as Cephalins Found in brain tissue and nerves involved in signal transduction activity Phosphoglycerides Phosphatidylinositol minor component of cell membrane Phosphatidylinositol 4,5- bisphosphates (PIP2), serve as signaling molecules in chemical communication Sphingolipids 1. Sphingomyelins major component of myelin sheaths in nerve cells Sphingosine (amino alcohol)serve as the head structure Ceramides are the simplest compound in this class Sphingolipids Ceramides create a skin barrier that helps prevent moisture loss Sphingolipids 2. Glycolipids (Glycosphingolipids) built on carbohydrate and ceramide (Cerebrosides) Cerebrosides contain at least one monosaccharide (glucose or galactose) Glucocerebrosides are found in macrophages (ingest and destroy foreign microorganisms) Sphingolipids 2. Glycolipids (Glycosphingolipids) Galactocerebrosides are found almost exclusively in the membranes of the brain cells Sphingolipids 2. Glycolipids (Glycosphingolipids) Gangliosides contain an oligosaccharide group (3 monosaccharides) These oligosaccharide groups always contain one or more molecules of N- acetylneuraminic acid (sialic acid)  STEROIDS a group of lipids that have fused- ring structure of 3 six-membered rings, and 1 five-membered ring derivatives of cholesterol Two major classes of steroid hormones: 1. Sex hormones - control reproduction and secondary sex characteristics 2. Adrenocorticoid hormones – control numerous biochemical processes in the body for metabolism  STEROID SEX HORMONES Androgen: male sex hormones Estrogens: female sex hormones - synthesized in the testes - synthesized in the ovaries - responsible for the - responsible for the development development of male secondary of female secondary sex sex characteristics characteristics and control of the - Testosterone menstrual cycle  ADRENOCORTICOID HORMONES produced by adrenal glands Mineralocorticoids: control the balance of Na and K ions in cells Glucocorticoid: control glucose metabolism and counteract inflammation  EICOSANOIDS arachidonic acid (20:4) derivatives Have profound physiological effects at extremely low concentrations. Short-lived hormone-like molecules Names are based on ring substituents and number of side- chain double bonds  EICOSANOIDS Thromboxanes cyclic ether ring and oxygen- containing functional groups promote platelet aggregation Leukotrienes derivative containing three conjugated double bonds and hydroxyl groups promote inflammatory and hypersensitivity (allergy) responses  Physiological Effects of Eicosanoids: 1. Blood Clotting Thromboxane A2 stimulates constriction of blood vessels and platelet aggregation Prostacyclin (PGI2) dilates blood vessels and inhibits platelet aggregation 2. Inflammatory Response Prostaglandins mediate aspects of inflammatory response 3. Reproductive system Stimulation of smooth muscle by PGE2  Physiological Effects of Eicosanoids: 4. Gastrointestinal tract Prostaglandins inhibit gastric secretion Prostaglandins increase the secretion of protective mucus Inhibition of hormone-sensitive lipases 5. Kidneys Prostaglandins dilate renal blood vessels Results in increased water and electrolyte excretion 6. Respiratory tract Leukotrienes promote the constriction of bronchi Prostaglandins promote bronchodilation  EICOSANOIDS Prostaglandins are synthesized from arachidonic acid by either (cyclooxygenase) COX-1 or COX-2 and play an important role in maintaining homeostasis in many body tissues.  BILE ACIDS Bile acids are polar derivatives of cholesterol made in the liver, that act as detergents in the intestine, emulsifying dietary fats to make them more accessible to digestive enzymes. Because they are eliminated in the feces, bile salts remove excess cholesterol in two ways: (1) They are themselves breakdown products of cholesterol (so cholesterol is eliminated via bile salts), and (2) they solubilize deposited cholesterol in the form of bile salt–cholesterol particles.  SAPONIFIABLE VS NONSAPONIFIABLE LIPIDS Saponifiable Lipid: A lipid that undergoes hydrolysis in a basic solution to yield 2 or more small molecules. Saponification is possible in molecules that contain the following linkages (bonds): LIPIDS Ester, Amide and Glycosidic SAPONIFIABLE NONSAPONIFIABLE Triacylglycerols Cholesterol Glycerophospholipids Bile acids, Sphingophospholipids Steroid hormones Sphingoglycolipids Eicosanoids Biological waxes  Biological Membranes Cells are surrounded by plasma membranes: Separates aqueous interior of a cell from the aqueous environment surrounding the cell The presence of cholesterol is characteristic of animal rather than plant membranes Bilayer: Nonpolar tails of phospholipids in the middle and polar heads are on the surface The membrane is a liquid-like structure due to unsaturation in lipid tails  FLUID MOSAIC MODEL Fluid: there is lateral motion of components in the membrane; proteins, for example, “float” in the membrane and can move along its plane Mosaic: components in the membrane exist side-by-side as separate entities the lipid bilayer is structured with proteins, glycolipids, and steroids such as cholesterol embedded in it Biological Membranes Cholesterol molecules are also components of plasma membranes: Cholesterol helps regulate membrane fluidity – The fused ring system does not allow rotation of fatty acid tails in the vicinity Fits between fatty acid chains of the lipid bilayer: Make it rigid Cholesterol thus acts a membrane plasticizer Biological Membranes The cell membranes also contain PROTEINS: Responsible for moving substances such as nutrients and electrolytes across the membrane Receptors for hormones and neurotransmitters Act as markers: process by which different cells recognize each other  Biological Membranes Types of Membrane Proteins: Integral Proteins: proteins embedded within the lipid bilayers contains hydrophobic residues (side chains) Ex. rhodopsin Peripheral Proteins: loosely bound outside the cell membrane have polar or electrostatic interactions Ex. Cytochrome C  Membrane Function: Membrane Transport Passive transport driven by a concentration gradient simple diffusion: a molecule or ion moves through an opening facilitated diffusion: a molecule or ion is carried across a membrane by a carrier/channel protein Active transport a substance is moved against a concentration gradient primary active transport: transport is linked to the hydrolysis of ATP or other high-energy molecule; for example, the Na+/K+ ion pump secondary active transport: driven by H+ gradient Lipid-Soluble Vitamins Vitamins are divided into two classes: lipid-soluble and water-soluble Lipid-Soluble Vitamins Vitamins are divided into two classes: lipid-soluble and water-soluble Lipid-Soluble Vitamins Vitamin A (Retinol) occurs only in the animal Extensively unsaturated hydrocarbon ( -carotene) Vitamin A is found in the plant world in the form of a provitamin in a group of pigments called carotenes enzyme-catalyzed cleavage of  - carotene followed by reduction gives two molecules of vitamin A  Lipid-Soluble Vitamins Vitamin A participates in the visual cycle in rod cells the active molecule is retinal (vitamin A aldehyde) retinal forms an imine with an -NH2 group of the protein opsin to form the visual pigment called rhodopsin the primary chemical event of vision in rod cells is absorption of light by rhodopsin followed by isomerization of the 11-cis double bond to the 11- trans double bond  Lipid-Soluble Vitamins A group of structurally related compounds that are involved in the regulation of calcium and phosphorus metabolism - the most abundant form in the circulatory system is vitamin D3  Lipid-Soluble Vitamins The most active of vitamin E is - tocopherol Vitamin E is an antioxidant; traps HOO and ROO radicals formed as a result of oxidation by O2 of unsaturated hydrocarbon chains in membrane phospholipids Lipid-Soluble Vitamins Vitamin K has an important role in the blood-clotting process Long unsaturated hydrocarbon side consists of repeating isoprene units required to modify prothrombin and other proteins involved in the clotting process References Bettelheim, F.A., Brown, W.H., Campbell, M.K., Farrell, S.O., & Torres, O. (2019). Introduction to General, Organic and Biochemistry. 12th Edition. Cengage Learning Campbell M., Farrell S., McDougal O. (2018). Biochemistry. 9th Edition. Cengage Learning Denniston, K. J., Topping, J.J., Quirk Dorr, D.R., & Caret, R.L. (2020). General, organic and biochemistry. 10th Edition. USA. McGraw Hill. Smith, J. (2022). General, organic and biochemistry (5th ed.). USA. McGraw Hill. ISBN10: 1260732029 Stoker, S.H. (2016). General, organic, and biological chemistry. 7th Edition. Cengage Learning