Lecture 01- Composition, Structure, and Functions of Lipids PDF

COMPOSITION, STRUCTURE AND Dr Ureshani Karunarathna FUNCTIONS OF LIPIDS Lesson Leaning outcomes At the end students should be able to, Describe the general structure of lipids Classify lipids and Fatty acids Describe the physiochemical properties of lipids Describe the funct...

COMPOSITION, STRUCTURE AND Dr Ureshani Karunarathna FUNCTIONS OF LIPIDS Lesson Leaning outcomes At the end students should be able to, Describe the general structure of lipids Classify lipids and Fatty acids Describe the physiochemical properties of lipids Describe the functions of lipids Outline the clinical significance of lipids Lipids Heterogenous group of organic substances in plant and animal tissues “Compounds which are relatively insoluble in water, but freely soluble in nonpolar organic solvents like benzene, chloroform, ether, hot alcohol, acetone, etc.” Consists of carbon, hydrogen and oxygen. Made up of – fatty acids and glycerol. GLYCEROL is an alcohol with three carbons, five hydrogens, and three hydroxyl (OH) groups. FATTY ACIDS Fatty acids are aliphatic carboxylic acids The general formula, R—CO—OH COOH (carboxylic group) represents the functional group. Depending on the R group (the hydrocarbon chain), the physical properties of fatty acids may vary. Classification of fatty acids 1. Depending on total number of carbon atoms: 2. Depending on length of hydrocarbon chain: 3. Depending on nature of hydrocarbon chain:  Classification of fatty acids 1. Depending on total number of carbon atoms: a. Even chain: They have carbon atoms 2,4,6 and similar series. Most of the naturally occurring lipids contain even chain fatty acids. b. Odd chain: They have carbon atoms 3, 5, 7, etc. Odd numbered fatty acids are seen in microbial cell walls. They are also present in milk. FATTY ACIDS 2. Depending on length of hydrocarbon chain: a. Short chain with 2 to 6 carbon atoms b. Medium chain with 8 to 14 carbon atoms c. Long chain with 16 and above, usually up to 24 carbon atoms d. Very long chain fatty acids (more than 24 carbon). FATTY ACIDS 3. Depending on nature of hydrocarbon chain: a. Saturated fatty acids -Only single bonds b. Unsaturated fatty acids Monounsaturated (monoenoic) -single double bond Polyunsaturated (polyenoic) - with 2 or more double bonds. c. Branched chain fatty acids d. Hydroxy fatty acids FATTY ACIDS FATTY ACIDS SATURATED FATTY ACIDS They have the general formula CH3-(CH2)n-COOH. For example, Acetic acid CH3—COOH Butyric acid CH3(CH2)2—COOH Palmitic acid CH3—(CH2)14—COOH Stearic acid CH3—(CH2)16—COOH FATTY ACIDS UNSATURATED FATTY ACIDS The presence of at least one double bond in a fatty acid makes it unsaturated. Those containing two or more double bonds are termed polyunsaturated fatty acids (PUFA). Unsaturated fatty acids exhibit geometrical isomerism at the double bonds FATTY ACIDS Isomerism a. Geometric Isomers: They depend on the orientation of the radicals around the axis of the double bonds. If the radicals are on the same side of the bond, it is called as ‘cis’ form. If the radicals are on the opposite side, a ‘trans’ form is produced. ‘Cis’ form is comparatively unstable and is more reactive. Example: Oleic acid and elaidic acid both have same molecular formula –C17H33COOH b. Positional Isomers: A variation in the location of the double bonds along the unsaturated fatty acids chain produces isomer of that compound. Thus, oleic acid could have 15 different positional isomers. FATTY ACIDS  The cis configuration of fatty acid double bonds is predominant in most plant and animal lipids. Trans variants, such as elaidic acid, are produced by processing (hydrogenation) and linked to cardiovascular disease. FATTY ACIDS Nomenclature of Fatty Acids Nomenclature is widely used to express the fatty acids by formula to indicate: The number of carbon atoms The number of double bonds and The positions of the double bonds. FATTY ACIDS Example; Oleic Acid (mol. formula C17H33 COOH) Oleic acid has one double bond between C9 and C10, thus: According to above criteria, it is expressed as 18 : 1; 9, [18 indicates the number of carbon atoms, 1 indicates the number of double bond and 9 indicates the position of the double bond]. FATTY ACIDS Systemic nomenclature Based on naming the fatty acids with the number of carbon atoms and Saturated acids end in “anoic” e.g. octanoic acid and Unsaturated acids with double bonds end in “enoic”, e.g. octadecenoic acid (oleic acid). FATTY ACIDS Omega () nomenclature: The omega () system is an alternative method for naming fatty acids. This method numbers carbon atoms from the methyl end of the fatty acid molecule. The Greek letter “” plus a numerical value indicates the position of the double bond. For example, linoleic acid contains 18 carbons with double bonds at atoms 9 and 12. The numerical designation of this fatty acid is C18:2Δ9,12. a linoleic acid is termed an 6 fatty acid using the omega system FATTY ACIDS Systematics and common names of fatty acids FATTY ACIDS ESSENTIAL FATTY ACIDS They cannot be synthesized in the body and must be provided in the diet. Lack of EFA in the diet can produce growth retardation and other deficiency manifestation symptoms. (found in plant oils), (found in fish oil) (found in fish and algal oils) FATTY ACIDS  Physical and Physiologic Properties of Fatty Acids Reflect Chain Length and Degree of Unsaturation The melting points of even-numbered carbon fatty acids increase with chain length and decrease according to unsaturation. A triacylglycerol containing three saturated fatty acids of 12 carbons or more is solid at body temperature, If the fatty acid residues are polyunsaturated, it is liquid to below 0C. FATTY ACIDS  In practice, natural acylglycerols contain a mixture of fatty acids tailored to suit their functional roles. For example, membrane lipids, which must be fluid at all environmental temperatures, are more unsaturated than storage lipids. Lipids in tissues that are subject to cooling, for example, in hibernators or in the extremities of animals, are also more unsaturated. FATTY ACIDS CLASSIFICATION OF LIPIDS 1. Simple lipids. 2. Compound lipids 3. Derived lipids.. 1. Simple lipids. They are esters of fatty acids with glycerol or other higher alcohols a. Fats are in the solid state at room temperature. Oils are fats in the liquid state at room temperature.. b. Waxes: Esters of fatty acids with higher molecular weight monohydric alcohols. Physiochemical properties of Triacylglycerols i. They are hydrophobic and insoluble in water. ii. Oils are liquids at 20oC; they are triacylglycerols, which contain a higher proportion of unsaturated fatty acids or short chain triglycerides. Oils are generally of plant origin. iii. Fats are solids at room temperature and contain mainly saturated long chain fatty acids. Fats are mainly of animal origin. iv. When the constituent fatty acids have a higher chain length and are predominantly saturated, ‘hard fat’ is formed, e.g. pig fat. v. Fats containing medium chain triacylglycerols or unsaturated fatty acids are soft fats, e.g. butter, coconut oil. Coconut oil contains mainly medium chain TAG, e.g. Lauric and Myristic acids. TRIACYLGLYCEROLS 2. Compound lipids They are fatty acids esterified with alcohol; but in addition, they contain other groups. a. Phospholipids: Lipids containing (in addition to fatty acids and an alcohol) a phosphoric acid residue. a. They frequently have nitrogen-containing bases (eg, choline) and other substituents. b. In many phospholipids the alcohol is glycerol (glycerophospholipids), c. but in sphingophospholipids it is sphingosine, which contains an amino group..b. Glycolipids (glycosphingolipids): Lipids containing a fatty acid, sphingosine, and carbohydrate. (Sugar containing lipids) c. Other complex lipids: Lipids such as sulfolipids and amino lipids. Lipoproteins may also be placed in this category. Glycolipids The glycolipids are sugar (galactosyl- and glucosyl) containing lipids oligosaccharides covalently attached to lipids N-acetylgalactosamine, N-acetylglucosamine and sialic acids required for processes such as signaling, cell adhesion or intercellular interactions. Glycolipids acts as blood group determinants  When both simple and compound lipids combine and undergo the process of hydrolysis, the produced 3. Derived lipids- chemical is known as the derived lipids These include fatty acids, glycerol, steroids, other alcohols, fatty aldehydes, ketone bodies, hydrocarbons, lipid-soluble vitamins and micronutrients. Because they are uncharged, acylglycerols (glycerides), cholesterol, and cholesteryl esters are termed neutral lipids.  Sterols, or steroid alcohols, are a type of plasma membrane lipid, ex. Cholesterol cholesterol is composed of a steroid backbone that results in a planar and more rigid molecule. Like phospholipids, cholesterol is amphipathic. It has a polar head that contains a hydroxyl group, whereas the rest of the molecule is hydrophobic, Functions of Lipids 1. Storage form of energy triglycerides high energy value – 9 kcal/g protein and carbohydrates 4 kcal/g 2. Structural components of bio membranes (phospholipids and cholesterol) 3. Metabolic regulators (steroid hormones and prostaglandins) 4. Provide insulation against changes in external temperature (subcutaneous fat) 6. Give shape and contour to the body 7. Protect internal organs by providing a cushioning effect (pads of fat) 8. Help in absorption of fat-soluble vitamins (A, D, E and K)  9. Improve taste and palatability of food. 10. Act as surfactants, detergents and emulsifying agents (amphipathic lipids) Pulmonary surfactant is a complex mixture of phospholipids (PL) and proteins (SP) that reduce surface tension at the air-liquid interface of the alveolus. 1. Storage of Energy as Fat The triacylglycerols are the storage form of lipids in the adipose tissue. (A connective tissue that stores excess calories as fat cells or adipocytes.) When stored as TAG, water molecules are repelled, and space requirement is minimal. In a 70 kg normal person, body stores contain about 11 kg of triacylglycerol, which is roughly equivalent to 100,000 kcal. If the same calories were stored as hydrated glycogen, the total weight of this alone would have been 65 kg! Excess fat in the body leads to obesity. TRIACYLGLYCEROLS 2. Structural components of bio membranes (phospholipids and cholesterol) Cell membranes are composed of lipids, proteins and sugars This structure is generally referred to as the phospholipid bilayer PHOSPHOLIPIDS Are the main lipid constituents of membranes Phospholipids in general are amphipathic, - have both hydrophobic and hydrophilic portion in their molecule Phosphatidylcholines (Lecithins) Glycerophospholipids containing choline (phosphatidylcholines, commonly called lecithins) are the most abundant phospholipids of the cell membrane and represent a large proportion of the body’s store of choline. Choline is important in nervous transmission, as acetylcholine PHOSPHOLIPIDS Sphingomyelins Sphingomyelins are found in the outer layer of the cell membrane lipid bilayer They are also found in large quantities in the myelin sheath that surrounds nerve fibers. They are believed to play a role in cell signaling and in apoptosis (programmed cell death). Sphingomyelins contain no glycerol, and on hydrolysis they yield a fatty acid, phosphoric acid, choline, and sphingosine PHOSPHOLIPIDS Phosphatidylethanolamine (cephalin) and phosphatidylserine Phosphatidylethanolamine (cephalin) and phosphatidylserine are found in cell membranes Phosphatidylserine found in most tissues Phosphatidylserine also plays a role in apoptosis. PHOSPHOLIPIDS Phosphatidylinositol Phosphorylated phosphatidylinositols (phosphoinositides) are minor components of cell membranes, but play an important part in cell signaling and membrane trafficking. PHOSPHOLIPIDS Cardiolipin (Phosphatidylglycerol) This phospholipid is found only in mitochondria Essential for the mitochondrial function. Decreased cardiolipin levels or alterations in its structure or metabolism cause mitochondrial dysfunction in aging and in pathological conditions it will cause heart failure, hypothyroidism, and Barth syndrome (cardioskeletal myopathy). PHOSPHOLIPIDS Main functions of lipids in cell membrane Fluidity Selective permeability Shape Signaling 1. Fluidity of cell membrane CHOLESTEROL influences the at high At high cholesterol can be fluidity of the temperatures it temperatures, membrane, and it cholesterol’s flat, thought of as a decreases fluidity does so in a and at low rigid structure buffering molecule bidirectional temperatures it limits in the membranes manner; phospholipid increases fluidity. movement. of animal cells that prevents abrupt changes in membrane fluidity over a range of temperatures. Fluidity of cell membrane THE LENGTH OF THE FATTY ACID TAIL The intermolecular interactions between the phospholipid tails add rigidity to the membrane. The longer the phospholipid tails, the more interactions between the tails are possible and the less fluid the membrane will be. Fluidity of cell membrane THE DEGREE OF SATURATION OF FATTY ACIDS TAILS Phospholipid tails can be saturated or unsaturated. Saturated tails have no double bonds and as a result have straight, unkinked tails. Unsaturated tails have double bonds and, as a result, have crooked, kinked tails. Unsaturated fatty acids, on the other hand, have more distance between the tails and thus fewer intermolecular interactions and more membrane fluidity. Fluidity of cell membrane Fluidity of cell membrane TEMPERATURE At lower temperatures, phospholipids in the bilayer do not have as much kinetic energy and they cluster together more closely, increasing intermolecular interactions and decreasing membrane fluidity. At high temperatures the opposite process occurs, phospholipids have enough kinetic energy to overcome the intermolecular forces holding the membrane together, which increases membrane fluidity. 2. Membrane permeability Cell membrane has selective permeabilities and acts as a barrier (maintaining differences in composition between the inside and outside of the cell) Lipid soluble substances are transported via simple diffusion Non-lipid soluble substances are transported via protein channels present in the membrane as integral proteins a. Channels -movement of ions and small molecules b. Transporters 3. Shape Membranes Are Asymmetric Structures (inside-outside asymmetry ) Asymmetry of the phospholipids outer leaflet - choline-containing phospholipids-(phosphatidylcholine, sphingomyelin) Inner leaflet- Amino phospholipids (phosphatidylserine and phosphatidylethanolamine) Maintaining the biconcave disc-like shape in RBC 4. Cell signaling Plays key roles in cell–cell interactions and in transmembrane signaling (receptor function- in recognizing different ligand e.g. hormones) Ex. Sphingomyelins- contain no glycerol, and on hydrolysis they yield a fatty acid, phosphoric acid, choline, and sphingosine  Sphingomyelins are found in the outer layer of the cell membrane lipid bilayer They are also found in large quantities in the myelin sheath that surrounds nerve fibers. They are believed to play a role in cell signaling and in apoptosis (programmed cell death). Clinical applications 1. Excessive fat deposits cause obesity. Truncal obesity is a risk factor for heart attack. 2. Abnormality in cholesterol and lipoprotein metabolism leads to atherosclerosis and cardiovascular diseases. 3. In diabetes mellitus, the metabolisms of fatty acids and lipoproteins are deranged, leading to ketosis (Raised levels of ketone bodies in tissues.) Saponification When triacylglycerols are hydrolyzed by alkali, the process is known as saponification. The products are glycerol and soaps LIPID PEROXIDATION Peroxidation (auto-oxidation) of lipids exposed to oxygen It is responsible not only for deterioration of foods (rancidity), but also for damage to tissues in vivo (living) May be a cause of cancer, inflammatory diseases, atherosclerosis, and aging. Lipid peroxidation is a chain reaction providing a continuous supply of reactive oxygen species (ROS). Antioxidants can use to control and reduce lipid peroxidation Reading 1. Pamela C. Champe, Richard A. Harvey, Illustrated Biochemistry, J. Lippincot Company 2. Roberk Murray, Daryl K Granner, Peter A. Mayes, Victor W. Rodwell, Harper’s Biochemistry, Appleton and Lange, Lange Medical Publications, New York 3. William J. Marshall, Stephen K, Marshalls Clinical Biochemistry, Elsevier Health Sciences, 2008