Lipids (PDF)

LIPIDS  Lipids are hydrophobic, nonpolar molecules. They are soluble in nonpolar solvent. They are insoluble in polar solvents, such as water They are isolated from the other biological molecules by extracting them with nonpolar solvents. 3  Lipids 4  C...

LIPIDS  Lipids are hydrophobic, nonpolar molecules. They are soluble in nonpolar solvent. They are insoluble in polar solvents, such as water They are isolated from the other biological molecules by extracting them with nonpolar solvents. 3  Lipids 4  Categories based on biochemical function: ▪ Energy-storage lipids ((triacylglycerol) ▪ Protective-coating lipids (biological waxes) ▪ Membrane Lipids (phospholipids, spingolipids, cholesterol) ▪ Emulsification lipids (bile acids) ▪ Messenger lipids (steroid hormones and eicosanoids) 5  Categories based on saponification Saponifiable lipids – converted to smaller molecules through hydrolysis Ex: Triacylglycerols, glycerophospholipids, spingophospholipids, spingoglycolipids, biological waxes Nonsaponifiable lipids –cannot be broken up into smaller units since they do not react with water Ex: Cholesterol, bile acids, Steroid hormones, eicosanoids 6  FATTY ACIDS 7  Fatty Acids Fatty Acids- naturally occuring monocarboxylic acids Fatty acids contain a carboxylic acid group They have a polar end in solution However, they also contain a long hydrocarbon tail Which overall, makes them nonpolar. nonpola pola r r 8  Fatty Acids Fatty acids typically contain between 12 and 20 carbons The number is usually always even nonpola pola r r The nonpolar tails interact with London forces. Rarely found free in nature but as part of lipids 9  Fatty Acids saturated monounsaturated polyunsaturated polyunsaturated 1 0  Fatty Acids The shortest descriptions (shorthand system/notation)of fatty acids include only the number of carbon atoms and double bonds in them (e.g. C18:0 or 18:0). C18:0 means that the carbon chain of the fatty acid consists of 18 carbon atoms and there are no (zero) double bonds in it, whereas C18:1 describes an 18-carbon chain with one double bond in it. What is the notation for this FA? nonpola pola r r 1 1  Fatty Acids Each double bond can be either in a cis- or trans- conformation and in a different position with respect to the ends of the fatty acid, therefore, not all C18:1s, for example, are identical. If there is one or more double bonds in the fatty acid, it is no longer considered saturated, rather it makes it mono- or polyunsaturated. 1 2  Fatty Acids Unsaturated fatty acids are of similar form, except that one or more alkenyl functional groups exist along the chain, with each alkene substituting a singly- bonded " -CH2-CH2-" part of the chain with a doubly-bonded "-CH=CH-" portion (that is, a carbon double bonded to another carbon). The two next carbon atoms in the chain that are bound to either side of the double bond can occur in a cis or trans configuration. 1 3  Fatty Acids 1 4  Fatty Acids cis/trans-Delta-x or cis/trans-Δx: The double bond is located on the xth carbon-carbon bond, counting from the carboxyl terminus. The cis or trans notation indicates whether the molecule is arranged in a cis or trans conformation. 1 5  Fatty Acids The cis or trans notation indicates whether the molecule is arranged in a cis or trans conformation. 1 6  Fatty Acids Saturated fatty acids do not contain any double bonds or other functional groups along the chain. The term "saturated" refers to H, in that all carbons (apart from the carboxylic acid [-COOH] group) contain as many hydrogens as possible. In other words, the omega (ω) end contains 3 hydrogens (CH3-) and each carbon within the chain contains 2 hydrogen 1 7  Fatty Acids A cis configuration means that the two connected carbons (on the C=C bond) are on the same side of the double bond. The rigidity of the double bond freezes its conformation and, in the case of the cis isomer, causes the chain to bend and restricts the conformational freedom of the fatty acid. 1 8  Fatty Acids 1 9  Fatty Acids Omega-x or ω-x : A double bond is located on the xth carbon-carbon bond, counting from the ω, (methyl carbon) end of the chain. Sometimes, the symbol ω is substituted with a lowercase letter n, making it n-6 or n-3. 2 0  Fatty Acids 2 1  Fatty Acids 2 2  Fatty Acids Melting points for saturated fatty acids: Melting Temperature {°C} No. of Carbons 2 3 4 2 Saturated fatty acids  Fatty Acids 2 5  Fatty Acids MONO unsaturated 2 6  Fatty Acids The more double bonds the chain has in the cis configuration, the less flexibility it has. When a chain has many cis bonds, it becomes quite curved in its most accessible conformations. For example, oleic acid, with one double bond, has a "kink" in it, 2 7  Fatty Acids while linoleic acid, with two double bonds, has a more pronounced bend. 2 8  Fatty Acids Linolenic acid, with three double bonds, favors a hooked shape. 2 9  Fatty Acids The effect of this is that in restricted environments, such as when fatty acids are part of a phospholipid in a lipid bilayer, or triglycerides in lipid droplets, cis bonds limit the ability of fatty acids to be closely packed and therefore could affect the melting temperature of the membrane or of the fat. 3 0  Fatty Acids Normally the double bonds are cis This lowers the melting points for fatty acids containing double bonds. (London forces) Melting Temperature {°C} No. of Double Bonds 3 1  Fatty Acids A trans configuration, by contrast, means that the next two carbon atoms are bound to opposite sides of the double bond. As a result, they don't cause the chain to bend much, and their shape is similar to straight saturated fatty acids. 3 2  Fatty Acids As acids, the carboxylic acid group in fatty acids can react with a base to produce a carboxylate ion By donating its proton (H+) to the base the fatty acid becomes negatively charged. We will talk more about acids and bases in Unit 6 3 3  Fatty Acids In most naturally occurring unsaturated fatty acids, each double bond has 3n carbon atoms after it, for some n, and all are cis bonds. 3 4 3 5  Fatty Acids Most fatty acids in the transconfiguration (trans fats) are not found in nature and are the result of human processing (eg, hydrogenation). 3 6  Fatty Acids 3 7  Fatty acids The human body is capable of synthesizing most fatty acids from carbohydrates or other fatty acids. Humans do not synthesize sufficient amounts of fatty acids that have more than one double bond. More than one double bond fatty acids are called essential fatty acids and they must be provided by the diet. Linoleic acid linolenic acid  Essential Fatty acids Omega-n acids n: the position of the first double bond Linoleic acid is called an omega-6 acid, because of the position of the first C=C in the nonpolar chain.  Essential Fatty acids Linolenic acid is called an omega-3 acid, because of the position of the first C=C in the nonpolar chain.  Fatty Acids The differences in geometry between the various types of unsaturated fatty acids, as well as between saturated and unsaturated fatty acids, play an important role is biological processes, and in the construction of biological structures (such as cell membranes). 4 1  ENERGY STORAGE LIPIDS: TRIACYLGLYCEROLS 4 2  Triacylglycerols (Triglycerides) Triacylglycerols are: Fats and oils (are stored in the body). Triesters of glycerol. Produced by Fischer esterification. Formed when the hydroxyl groups of glycerol react with the carboxyl groups of fatty acids.  Esterification glycerol three fatty acids triacylglycerol + 3H2O Acid  Triacylglycerols (Triglycerides) CH2 OH CH OH Glycerol CH2 OH G Fatty acid L Y C Fatty acid E R O L Fatty acid Produced by esterification of glycerol (a trihydroxyl alcohol).  Triacylglycerols (Triglycerides) Simple triacylglycerols have three identical fatty acid side chains. Mixed triacylglycerols have two or three different fatty acids.  Triacylglycerols (Triglycerides) Saturated triacylglycerols contain only saturated fatty acids. Monounsaturated triacylglycerols have 1 C=C bond. Polyunsaturated triacylglycerols have many C=C bonds. Increasing the number of double bonds in the fatty acid chain decreases the melting point of the triacylglycerol.  Triacylglycerols (Triglycerides) Fat: is a triacylglycerol that is solid at room temperature. Made by more saturated fatty acids (Saturated triacylglycerols). Meat, milk, butter and cheese (animal sources). Oil: is a triacylglycerol that is liquid at room temperature. Made by more unsaturated fatty acids (Unsaturated triacylglycerols). Corn, cotton seed, safflower and sunflower (plant sources). Both are colorless, odorless, and tasteless. 4 9  Fat & Health - Fats are used to build cell membranes, insulate the body, and store energy for later use. - It is recommended that no more than 20-35% of a person’s caloric intake should come from lipids. - A high intake of saturated triacylglycerols is linked to heart disease. - Saturated fats stimulate cholesterol synthesis in the liver, which can lead to cholesterol plaques building up inside arteries. - The result is high blood pressure, heart attack, and even stroke. - Unlike other vegetable oils, oils from palm and coconut trees are very high in saturated fats.  Fat & Health - Unsaturated triacylglycerols (omega-3 fatty acids from fish) lower the risk of heart disease by decreasing the level of cholesterol in the blood. - However, if the double bond of the unsaturated triacylglycerol is trans, the beneficial effect is lost. - Trans fats, which are primarily synthesized instead of naturally occurring, act like saturated fats and increase the cholesterol levels in the blood.  1- Hydrogenation - Hydrogen adds to the double bonds of unsaturated fats (using transition metal catalyst such as Ni). H H H H Ni _ C=C + H2 → _C_C_ _ - Melting point is increased. H H - Liquid oils are converted to semi-solid fats.  Reactions of Triglycerides 5 3 1- Hydrogenation Ni _ _ + 3H2 glyceryl Trioleate (triolein) glyceryl tristearate (tristearin)  2- Hydrolysis Triacylglycerols are hydrolysis (split by water) in the presence of strong acid or lipase (digestive enzyme). + 3H2O H H + 3HO H+ or Lipase H  Metabolism of tricaylglycerols - Humans store energy as triacylglycerols in adipose cells below the surface of the skin, in the breast area, and surrounding internal organs. - The number of adipose cells is constant; weight gained or lost causes them to swell or shrink, but not decrease or increase in number. - To metabolize triacylglycerols for energy, the esters are hydrolyzed by enzymes called lipases. - Complete metabolism of a triacylglycerol yields CO2, H2O, and a great deal of energy.  3- Saponification (Basic Hydrolysis) - Is the process of forming “soaps” (salts of fatty acids). - Is the reaction of a fat with a strong base (NaOH). - Splits triacylglycerols into glycerol and the salts of fatty acids. - With KOH or the oils that are polyunsaturated gives softer soaps (liquid soaps). - Soaps are typically made from lard (from hogs), tallow (from cows or sheep), coconut oil, or palm oil. - All soaps work in the same way, but have different properties depending on the lipid source, length of C chain, and degree of unsaturation. 3- Saponification (Basic Hydrolysis) + 3NaOH H Heat H + 3 Na+-O “soap” Salt of fatty acid H  Soaps Hydrophobic part: nonpolar Hydrophilic part: polar (remains in contact with environment)  Soaps When soap is mixed with dirt (grease, oil, and …), soap micelles “dissolve” these nonpolar, water-insoluble molecules.  4. Oxidation Oxidation breaks double bonds , producing aldehyde or carboxylic acid products. (Oil turning rancid) 6 1 6 2  Protective-coating lipids: Biological Waxes 6 3  Waxes Wax is an ester of saturated fatty acid and long chain alcohol. Ester bond Long-chain alcohol Fatty acid Acid  Waxes For example, shown below is the formation of spermaceti wax, isolated from the heads of sperm whales. Acid  Waxes Because of their long nonpolar C chains, waxes are very hydrophobic. O Beeswax CH3(CH2)14 C O(CH2)29CH3 (myricyl palmitate) hydrophobic hydrophobic region region They form protective coatings: - In plants, they help prevent loss of water and damage from pests. - In humans and animals, provide waterproof coating on skin and fur.  Beeswax Carnauba Coating Jojoba Lanolin from wool lotions  Waxes Hydrolysis reaction: like other esters, waxes are hydrolyzed. Heat  Membrane lipids: Phospholipids and Glycolipids 6 9  Phospholipids and Glycolipids Phospholipids and Glycolipids are the stuff that biological membranes are made of. Like the soaps, these molecules are highly aphipathic, and when mixed with water spontaneously form membranes that are described as lipid bilayers. 7 0  Phospholipids and Glycolipids Soaps form Phospholipids form Micelles Lipid Bilayers 7 1  Phospholipids and Glycolipids There are two types of phospholipids Glycerophospholipids 7 2  Phospholipids and Glycolipids There are two types of phospholipids Sphingophospholipids (sphingolipids) 7 3  Phospholipids and Glycolipids The Glycerophospholipids have a structure similar to triglycerides, with one of the fatty acids replaced with a phosphate. There is usually an additional alcohol attached to the other side of the phosphate 7 4  Phospholipids and Glycolipids The Glycerophospholipids have a structure similar to triglycerides, with one of the fatty acids replaced with a phosphate. phosphoester bonds 7 5  Phospholipids and Glycolipids The Glycerophospholipids have a structure similar to triglycerides, with one of the fatty acids replaced with a phosphate. “Phosphotidyl-” refers to everything but the X 7 6  Phospholipids and Glycolipids Phospholipids are used commercially as emulsifying agents. An emulsifying agent stabilizes an emulsion. An emulsion is a colloidal suspension of one liquid in another. ‣ An example is mayonnaise, which is a colloidal suspension of oil and water. Lecithin, which is another name for the phospholipid phosphotidylcholine, is used as an emulsifying agent in mayonnaise and other prepared foods. 7 7  Phospholipids and Glycolipids The sphingolipids function similarly to the glycerophospholipids, but structurally they are different. There is not glycerol core The glycerol and one of the fatty acids found in glycerophospholipids is replaced with a molecule called sphingosine. 7 8  Phospholipids and Glycolipids Phosphospholipids The sphingolipids are found in the myelin membranes that insulate the nerve cells. Some sphingolipids use sugars for the alcohol portion of the molecule These are called glycolipids. 7 9  Cell Membrane Carbohydrate Phospholipid bilayer Nonpolar Hydrophobic Polar Hydrophilic Semipermeable: selected nutrients can enter and waste products can leave. Fluid mosaic model  Cell Membrane - Peripheral proteins are embedded within the membrane and extend outward on one side only. - Integral proteins extend through the entire bilayer. - Sometimes carbohydrates are attached to the exterior of the cell forming glycolipids and glycoproteins.  Transport Across a Cell Membrane Simple Diffusion: Small molecules like O2 and CO2 can diffuse through the cell membrane, traveling from higher to lower concentration. Facilitated Transport: Larger polar molecules (glucose) and ions (Cl - and HCO3-) travel through integral protein channels. Active Transport: Other ions, Na+, K+, and Ca2+, move against the concentration gradient; this required energy input.  Steroids Steroids have: A steroid nucleus which is 4 carbon rings. Attached groups that make the different types of compounds. (steroid nucleus) No fatty acids.  Cholesterol Cholesterol: Is the most abundant steroid in the body. Insoluble in water (need a water soluble carrier). Has methyl CH3- groups, alkyl chain, and -OH attached to the steroid nucleus.  Cholesterol Cholesterol: Is obtained from meats, milk, and eggs. Is synthesized in the liver from fats, carbohydrates and proteins. Is needed for cell membranes, brain and At artery clogged by cholesterol plaque nerve tissue, steroid hormones, and Vitamin D. Clogs arteries when high levels form plaque (because it is insoluble in blood). No cholesterol in vegetable and plants. Gallstones form in gallbladder  Lipoproteins Triacylglycerols Water-soluble form of lipids (soluble in blood) Spherical particles Polar surface and nonpolar inner Transporting lipids through the bloodstream to tissues where they are stored, Used for energy, or to make hormones.  Lipoproteins VLDL: very-low-density lipoprotein Triglycerides and Cholesterol LDL: low-density lipoprotein (bad Cholesterol) Cholesterol HDL: high-density lipoprotein (good Cholesterol) Cholesterol Recommended levels are: HDL > 40 mg/dL, LDL < 100 mg/dL, total serum cholesterol < 200 mg/dL. Chylomicrons Triglycerides and Cholesterol VLDL Heart Fat and Liver storage muscle Intestine cells Energy s and elimination HDL LDL MESSENGER LIPIDS  Steroid Hormones A hormone is a molecule that is synthesized in one part of an organism, which then elicits a response at a different site. Two types of steroids hormones: 1. Sex hormones Estrogens & progestins in females Androgens in males 2. Adrenal Cortical Steroids  Sex Hormones Estrogens (Female Sex Hormones): The estrogens estradiol and estrone control development of secondary sex characteristics, regulate the menstrual cycle, and are made in the ovaries.  Sex Hormones Progestins (Female Sex Hormones): The progestin progesterone is called the “pregnancy hormone”; it is responsible for the preparation of the uterus for implantation of a fertilized egg.  Sex Hormones Androgens (Male Sex Hormones): Testosterone and Androsterone are androgens made in the testes. They control the development of secondary sex characteristics in males.  Sex Hormones - Synthetic androgen analogues, called anabolic steroids, promote muscle growth. - They have the same effect as testosterone, but are more stable, so they are not metabolized as quickly. - They have come to be used by athletes and body builders, but are not permitted in competitive sports. - Prolonged use of anabolic steroids can cause physical and psychological problems.  Sex Hormones Some examples of anabolic steroids: (THG or the Clear)  Adrenal Cortical Steroids Aldosterone regulates blood pressure and volume by controlling the concentration of Na+ and K+ in body fluids. Cortisone and cortisol serve as anti-inflammatory agents, which also regulate carbohydrate metabolism. aldosterone cortisone cortisol  Adrenal Cortical Steroids Cortisone are used to suppress organ rejection after transplant surgery and to treat many allergic and autoimmune disorders. Prolonged use of these steroids can have undesired side effects, including bone loss and high blood pressure. Prednisone, a synthetic alternative, has similar anti-inflammatory properties but can be taken orally.  Eicosanoids Prostaglandins and Leukotrienes are two types of eicosanoids (20 C atoms derived from the fatty acids). - All eicosanoids are very potent compounds, which are not stored in cells, but rather synthesized in response to external stimulus. - Unlike hormones they are local mediators, performing their function in the environment in which they are synthesized.  Prostaglandins Prostaglandins are carboxylic acids that contain a five-membered ring and have a wide range of biological activities.  Prostaglandins Prostaglandins are responsible for inflammation. - Aspirin and ibuprofen relieve pain and inflammation by blocking the synthesis of these molecules. - Prostaglandins also decrease gastric secretions, inhibit blood platelet aggregation, stimulate uterine contractions, and relax smooth muscles. - There are two different cylcooxygenase enzymes responsible for prostaglandin synthesis called COX-1 and COX-2.  Prostaglandins COX-1 is involved in the usual production of prostaglandins. COX-2 is responsible for additional prostaglandins in inflammatory diseases like arthritis. - Nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin and ibuprofen inactivate both COX-1 and -2, but increase risk for stomach ulcer formation. - Drugs sold as Vioxx, Bextra, and Celebrex block only the COX-2 enzyme without affecting gastric secretions.  Leukotrienes Asthma is characterized by chronic inflammation, so inhaled steroids to reduce this inflammation are commonly used. Leukotrienes are molecules that contribute to the asthmatic response by constricting smooth muscle of the lung. New asthma drugs act by blocking the synthesis of leukotriene C4, which treat the disease instead of just the inflammation symptoms.  Emulsification Lipids: Bile acids Bile acid – a cholesterol derivative that functions as a lipid- emulsifying agent in the aqueous environment of the digestive track Bile is a dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver 1 0  Emulsification Lipids: Bile acids Primary bile acids are those synthesized by the liver. Secondary bile acids result from bacterial actions in the colon. 1 0 The End