AS1 Lipids - Chemistry and Structure.pdf

LIPIDS: CHEMISTRY AND STRUCTURE Amos M Sakwe, Ph. D., MSCI School of Graduate Studies West Basic Sciences Bldg. Rm.# 2141B (Office), #3108 (Lab) Phone: 615-327-6064 Email: [email protected] Course Outline and expectations • • • • • • • • • • • Definition and types of lipids Various types of Fatty A...

LIPIDS: CHEMISTRY AND STRUCTURE Amos M Sakwe, Ph. D., MSCI School of Graduate Studies West Basic Sciences Bldg. Rm.# 2141B (Office), #3108 (Lab) Phone: 615-327-6064 Email: [email protected] Course Outline and expectations • • • • • • • • • • • Definition and types of lipids Various types of Fatty Acids Structure and nomenclature of Fatty Acids Physical Properties of Fatty acids Reactions involving lipids Structural composition of Lipids Simple lipids Complex lipids Derived lipids Functions of lipids Components of Cell membranes What are Lipids? Lipids are a chemically diverse group of compounds that are relatively insoluble in water but are soluble in nonpolar solvents. Types of Lipids Lipids can be classified into: • Simple Lipids (Storage Lipids)—The principal stored form of energy • Complex Lipids (Structural Lipids)– Are the major structural elements of biological membranes. • Lipid derivatives are signaling molecules and cofactors • The simplest form of lipids are Fatty Acids What are Lipids? Overview of Types of Lipids Structure and Nomenclature of Fatty Acids Unsaturated Fatty Acids Saturated Fatty Acids What are Fatty Acids? Fatty acids are carboxylic acids with long hydrocarbon chains. General formula: R-COOH Where R is a linear carbon chain with generally even number of carbons atoms. R with odd number of carbon atoms R with branched carbon atom chain H3C C H2 H2 C C H2 H2 C C H2 H2 C C H2 H2 C C H2 H2 C C H2 CH3-(CH2)16- COOH H2 C C H2 H2 C C H2 H2 C O C OH O R C OH Types of Fatty Acids Saturated Fatty Acids Unsaturated Fatty Acids Branched Chain Fatty Acids Nomenclature of Fatty Acids Systematic Nomenclature Fatty acids are named after the corresponding number of hydrocarbons: ▪ Final -e in the parent hydrocarbon is substituted by -oic Dodecane- CH3 –(CH2)10 –CH3 Dodecanoic acid- CH3 –(CH2)10 –COOH 12:0 12 carbon atom chain No double bonds Examples of Saturated Fatty Acids Most common No.of C atoms Common name Systemic Name (Formula) 2 Acetic Acid 4 Butyric Ethanoic acid (CH3COOH) Butanoic acid (CH3(CH2)2COOH) 6 Caproic Acid Hexanoic acid (CH3(CH2)4COOH) 12 Lauric Dodecanoic acid (CH3(CH2)10COOH) 14 Myristic Tetradecanoic acid (CH3(CH2)12COOH) 16 Palmitic Hexadecanoic acid (CH3(CH2)14COOH) 18 Stearic Octadecanoic acid (CH3(CH2)16COOH) Unsaturated Fatty Acids Unsaturated fatty acids contain one or more double bonds Named by adding enoic to the root name of the parent hydrocarbon Monounsaturated FAs - only one double bond e.g. Octadecenoic acid, with one double bond; Polyunsaturated Fatty Acids (PUFA) - two or more double bonds Octadecadienoic acid for two double bonds The double bonds in polyunsaturated fatty acids are separated by at least one methylene group. Nomenclature of Fatty Acids  No double bond: Octadecanoic acid (Stearic acid) 18:0 Saturated Fatty Acid  One double bond: Octadecenoic acid (Oleic acid) 18:1  Two double bonds: Octadecadienoic acid (Linoleic acid) 18:2  Three double bonds: Octadecatrienoic acid (Linolenic acid) 18:3 Unsaturated Fatty Acid Numbering of Fatty Acids • Two ways of numbering carbon atoms in fatty acid : • The ω or n-system: • The C-system: • The numbering begins with • Carbon atoms are the ω carbon numbered from the carboxy • Location of the first double terminus. bond from the ω-carbon • COOH = C1 (count from the methyl end) • Carbon atoms 2 and 3 are determines the fatty acid designated α and β carbons group. respectively • Two important omega fatty • The methyl group at the acids groups: end of the chain is Omega-6 (6) designated the ω carbon Omega-3 (3) Notation of Fatty Acids Monounsaturated Fatty Acids Carbon Chain Length Number of Double Bonds 18:1:9 or 18:1 (9) Position of Double Bonds Polyunsaturated Fatty Acids 18:3:9,12,15 or 18:3 (9,12,15) Polyunsaturated Fatty Acids 20:5()5,8,11,14,17 22:6()4,7,10,13,16,19 Omega system-Nomenclature of Fatty Acids • The location of the first double bond from the terminal CH3 group or the ω-carbon determines the group. • Two important omega fatty acids groups: Omega-6 (6) Omega-3 (3) Omega Fatty Acids 6 Linoleic acid C18:2; ω6  6   Arachidonic acid C20:4; ω6 3 Linolenic acid C18:3; ω3  3 Eicosapentaenoic acid (EPA) C20:5; ω3 Two Essential Fatty Acids • In mammals, double bonds can be introduced only up to the 9 position but never beyond. • -3 and -6 fatty acids must be derived from diet The two essential fatty acids, that must be derived from diet include: • Linoleic acid (LA): omega-6 fatty acid • -linolenic acid (LNA or ALA): omega-3 fatty acid Arachidonic acid An omega-6 fatty acid - synthesized from Linoleic acid 12 9 Linoleic acid Arachidonic acid Types of double bonds in Fatty Acids Two double bonds: Cis double bond in which the H atoms are oriented on the same side of the double bond Trans double bond in which the H atoms are oriented on opposite sides of the double bond Unsaturated Fatty Acids- Geometric Isomerism Cis Fatty Acids Oleic acid Arachidonic acid - Cis double bonds between carbons in the hydrocarbon tail, cause bends or ―kinks in the shape of the molecules. Double bonds in naturally occurring unsaturated fatty acids are mostly in the Cis- configuration Examples of Unsaturated Fatty Acids No. of C Atoms and Family No./Position of Common Double Bonds Monoenoic acids (one double bond) Common Name Systematic Name 18:1;9 9 Oleic cis-9-Octadecenoic 18:1;9 9 Elaidic trans-9-Octadecenoic Dienoic acids (two double bonds) 18:2;9,12 6 Linoleic all-cis-9,12-Octadecadienoic Trienoic acids (three double bonds) 18:3;6,9,12 6 γ-Linolenic (GLA) all-cis-6,9,12-Octadecatrienoic 18:3;9,12,15 3 α-Linolenic (ALA) all-cis-9,12,15-Octadecatrienoic Tetraenoic acids (four double bonds) 20:4;5,8,11,14 6 Arachidonic all-cis-5,8,11,14-Eicosatetraenoic Pentaenoic acids (five double bonds) 20:5;5,8,11,14,17 3 Timnodonic all-cis-5,8,11,14,17-Eicosapentaenoic (EPA) Hexaenoic acids (six double bonds) 22:6;4,7,10,13,16,19 Cervonic all-cis-4,7,10,13,16,19-Docosahexaenoic (DHA) 3 Physical properties of Fatty Acids Saturated fatty acids: • Molecules fit closely together in a regular pattern • High melting points makes them solids at room temperature. • As chain length increases, the melting point increases Physical properties of Fatty Acids Unsaturated fatty acids: • The cis double bonds with kinks in hydrocarbon tails do not allow molecules to stack closely. • Low melting points and are liquids at room temperature • As the number of double bonds increases, the melting point decreases Arachidonic acid 20 – 49.5 Lipid Peroxidation (Auto-oxidation) ➢ Lipid peroxidation is the oxidative degradation of lipids (lipids exposed to oxygen) ➢ Generation of free radicals that are highly reactive ➢ Free radicals containing oxygen (e.g. ROO•, RO•, OH•) are termed reactive oxygen species (ROS) ➢ Lipid peroxidation is a chain reaction that provides a continuous supply of ROS, which initiates further peroxidation ➢ Polyunsaturated fatty acids are the most susceptible to lipid peroxidation Lipid Peroxidation (Auto-oxidation) Lipid peroxide 1) Initiation 2) Propagation 3) Termination Lipid Peroxidation (Auto-oxidation) Harmful consequences of Lipid Peroxidation: ➢ Damage to tissues and may cause cancer ➢ Deterioration of food causing rancidity Control of Lipid Peroxidation ➢ Antioxidants control and reduce lipid peroxidation ➢Natural Antioxidants: ➢Lipid soluble ➢Vitamin E, ➢β-Carotene ➢Water soluble ➢Vitamin C ➢Food additives➢Butylated hydroxyanisole (BHA), ➢Butylated hydroxytoluene (BHT) Hydrogenation • • • • Hydrogenation- is the addition of H2 to double bonds of unsaturated fatty acids making them saturated (more solid). Increases stability - more resistant to oxidation Trans fats are formed during hydrogenation of unsaturated fatty acids. “Partially hydrogenated” oils contain higher levels of trans fats. Copyright © 2007 by Pearson Education, Inc Publishing as Benjamin Cummings Trans fats are associated with increased risk of cardiovascular disease. Steroids Lipids Fatty Acids Cholesterol Vitamins Bile salts Lipid Lipids Derivatives as signals Eicosanoids and cofactors Long-chain alcohol Waxes Simple Lipids Complex Lipids Eicosanoids • Derivatives of unsaturated fatty acid with 20 carbons e.g. Arachidonic acid. • This group includes the prostaglandins, thromboxanes and leukotrienes. Eicosanoids Prostaglandins: • First identified in Prostate glands; • Derived from Prostanoic acid; • These are hormone –like and act via 7 transmembrane receptors to cause muscle contraction and relaxation, inflammation, platelet aggregation , decrease blood pressure and suppress gastric secretions. Thromboxanes: First isolated from platelets or thrombocytes; Promote platelet aggregation or thrombus formation at sites of injury. Leukotrienes: Were initially described in Leucocytes; cause inflammation and allergic reactions Steroids Lipids Lipids Fatty Acids Cholesterol Vitamins Bile salts Lipids as signals Eicosanoids and cofactors Long-chain alcohol Waxes Simple Lipids Complex Lipids Simple Lipids (Storage Lipids) Esters of fatty acids with alcohols Formation of an ester: O R'OH + HO-C-R" Two types of Simple Lipids: • Triacylglycerols: Fats and Oils • Waxes O R'-O-C-R'' + H2O TRIACYLGLYCEROL-(TAG, triglycerides) • Tri-fatty acid esters of glycerol • Nonpolar, neutral lipids. • Types of triacylglycerols: 1. Simple triacylglycerols: The three fatty acids esterified to glycerol are of the same type. 2. Mixed triacylglycerols : The three fatty acids esterified to glycerol are of different types. – Most naturally occurring triacylglycerols are of the mixed type. TRIACYLGLYCEROLS • The major form of fats or oils – Fats are solid at room temperature – Oils are usually liquid at room temperature • Major storage form of lipids • Stored mostly in adipocytes Adipocytes TRIACYLGLYCEROLS • Triacylglycerols provide stored energy and insulation • They are a highly concentrated form of metabolic energy – Reduced – Anhydrous • They are NOT structural components of biological membranes Waxes Esters of long chain fatty acids (C14  C36) with long chain (C16  C36) monohydric alcohols. Long-chain alcohol • • • • Storage fuels for some microorganisms. Water repellent in animals. Prevents excess water evaporation in plants. Application in industries, pharmaceuticals, and cosmetics Steroids Steroids Lipids Lipids Fatty Fatty Acids Acids Cholesterol Cholesterol Vitamins Vitamins Bile Bilesalts salts Lipids Lipids as as signals signals Eicosanoids Eicosanoids and and cofactors cofactors alcohol Long-chain alcohol Long-chain Waxes Waxes Simple Simple Lipids Lipids Complex Complex Lipids Lipids Complex Lipids Head Group Head Group Head Group Glycerophospholipids/Phosphoglycerolipids Glycerol + 2 fatty acids + phosphate Glycerophospholipids 2 Fatty acids (C1 & C2) + phosphate (C3)1,2-diacylglycerol 3-phosphate- (Phosphatidic Acid/Phosphatidate) Glycerophospholipids are derivatives of Phosphatidic acid Nomenclature of Glycerophospholipids is determined by the Head group substituent. Types of Glycerophospholipids (Cephalin) (Lecithin) (Cephalin) (diphosphatidyl glycerol) Dipalmitoyl lecithin (Dipalmitoylphosphatidylcholine) A surface active agent is a major constituent of pulmonary surfactant Deficiency of Dipalmitoyl lecithin leads to Respiratory Distress Syndrome Plasmalogens An ether-linked (R-O-R’) hydrocarbon chain at C-1 of glycerol, instead of ester-linked fatty acid R-COO-R’. Ethers: general formula R–O–R‘ e.g. Phosphatidal choline -Choline -Ethanolamine -Serine (PAF) Found in Myelin and cardiac muscle PAF is involved in Platelet aggregation and degranulation. Complex Lipids Head Group Head Group Group Head Sphingophospholipids Sphingosine + 1 fatty acid + phosphate Sphingosine Sphingolipids contain Sphingosine, a long chain amino alcohol Sphingosine 3 2 1 3 2 1 Ceramide In Ceramides- the amino group of sphingosine is linked to the carboxyl group of fatty acid by an amide bond. Ceramide Ceramide is the parental structure of all sphingolipids. Sphingomyelin-Sphingophospholipid Sphingomyelin has predominantly a phosphocholine polar head group. Sphingomyelin • Sphingomyelin is present in plasma membranes and is especially abundant in the myelin sheath surrounding neurons. (Electrical Insulation of nerve fibers) • Sphingomyelin is similar in size and shape to phosphatidylcholine. Complex Lipids Head Group Head Group Glycolipids (Glycosphingolipids) Sphingosine + 1 fatty acid + Sugar Glc-Gal-NANA Cerebroside Globoside Ganglioside Cerebroside A cerebroside is a ceramide with a monosaccharide such as glucose or galactose as the polar head group. 1 2 3 Glucocerebroside (Glucosylceramide) Globosides • • Di, tri or tetrasaccharides (oligosaccharides). Lactosylceramide- contains glucose and galactose. Gangliosides • • • Ceramide with Complex oligosaccharide Contain one or more Sialic acid molecules. N-acetylneuraminic acid (NeuAc, NANA), is the major sialic acid. 1 2 3 GM2 ganglioside (contains two NANA molecules) Sialic acid Steroids Steroids Lipids Lipids Fatty Acids Fatty Acids Cholesterol Cholesterol Vitamins Vitamins Bile salts Bile salts Lipids Lipids signals Lipids asassignals Eicosanoidsand Eicosanoids derivatives and cofactors cofactors Long-chain alcohol Waxes Waxes Simple Lipids Complex Lipids Lipids Complex Steroids • Steroid nucleus consists of three cyclohexane rings (A, B, C) and one cyclopentane ring (D) fused together. Steroid nucleus Sterols • If the compound has one or more hydroxyl groups and no carbonyl or carboxyl groups, it is a sterol, and the name terminates in -ol. • Cholesterol is a major sterol Cholesterol Ergosterol Cholesterol • Cholesterol has a hydroxyl group at C-3 and a side chain at C-17. • It is a major component of cell Membranes and of plasma lipoproteins. Cholesterol • Occurs in animals but not in plants (Animal Sterol) or bacteria. • A precursor for the synthesis of bile salts, vitamin D and steroid hormones. • Cholesteryl ester- is a storage form of cholesterol in which the OH group on position 3 is esterified with a long-chain fatty acid. • Cholesterol is synthesized from acetyl CoA through simple fivecarbon subunits called isoprenes. Lipids derived from Isoprenoids (isoprene derivatives) Functions of Lipids • High Energy Value: Storage form of energy • Lipids are excellent insulators – Thermal insulation: protects from cold – Electrical insulation: protects nerves, help conduct electro-chemical impulses (myelin sheath) • Lipids are the structural components of cell membranes • Lipid derivatives are hormones and signaling molecules • Lipids have essential roles in nutrition – Essential fatty acids – Combinations of lipid and protein (lipoproteins) transport lipids and fat-soluble vitamins. Cell Membranes • Separate cellular contents from the external environment • Membranes organize cells into functionally distinct compartments • Important in cellular transport of molecules • Each type of cell has a unique membrane composition with varying percentages of lipids and proteins Membrane Lipids Are Amphipathic Amphipathic lipids when mixed with water form complexes in which polar regions are in contact with water and non-polar regions are away from water. • Hydrophilic heads (polar) form hydrogen bonds with water • Hydrophobic tails (non-polar) are excluded by water molecules Aggregates of amphipathic lipid molecules in an aqueous environment Cone-shaped lipid molecules form micelles Cylindrical lipids form bilayers Lipid bilayers spontaneously close to form a sealed compartment Cell membranes are a lipid bilayer - Hydrophobic end of the lipid molecules is directed towards the interior of the membrane - Hydrophilic end of the lipid molecules is directed towards the inside or outside of the cell. Bilayers are the key structures in biological membranes. Membrane Lipids Each Type of Membrane has a Characteristic Lipid composition Types of Lipids in Membranes: • Phospholipids • Glycolipids • Cholesterol Phospholipids are the most abundant membrane lipids The Membrane Bilayer Is Fluid Individual lipid molecules are able to diffuse freely within lipid bilayers The composition of a membrane regulates the degree of its fluidity • Membrane lipids with fatty acyl side chains that are saturated (no double bonds) pack tightly in the membrane and make it less fluid • Lipids that are unsaturated (with double bonds) pack loosely and make it more fluid The composition of a membrane regulates the degree of its fluidity The presence of cholesterol in the membrane helps in maintaining membrane fluidity Membrane lipids are asymmetrically distributed in the lipid bilayer Cell Membranes Fluid Mosaic Model Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings