Organic Chemistry Sixth Edition Chapter 29 Lipids PDF

Organic Chemistry Sixth Edition Janice Gorzynski Smith University of Hawai’i Chapter 29 Lipids Demetra...

Organic Chemistry Sixth Edition Janice Gorzynski Smith University of Hawai’i Chapter 29 Lipids Demetra Giuri ©2020 McGraw-Hill Education. All rights reserved. Authorized only for instructor use in the classroom. No reproduction or further distribution permitted without the prior written consent of McGraw-Hill Education. 1  Lipids Lipids are biomolecules that are soluble in organic solvents. The identity of lipids is defined on the basis of a physical property and not by the presence of a particular functional group. Lipids share many properties with hydrocarbons. Figure 29.1 Three examples of lipids ©2020 McGraw-Hill Education. 2  Hydrolyzability of Lipids Lipids can be categorized as hydrolyzable and nonhydrolyzable. Hydrolyzable lipids can be cleaved into smaller molecules by hydrolysis with water. Many hydrolyzable lipids contain an ester unit. Nonhydrolyzable lipids cannot be cleaved into smaller units by aqueous hydrolysis. ©2020 McGraw-Hill Education. 3  Hydrolyzable lipids Waxes Waxes are esters (RCOO R′) formed from a high molecular weight alcohol (R′OH) and a fatty acid (RCOOH). Lanolin, a wax composed of a complex mixture of high molecular weight esters, coats the wool fibers of sheep. Spermaceti wax, isolated from the heads of sperm whales, is largely CH3(CH2)14COO(CH2)15CH3. The three-dimensional structure of this compound shows how small the ester group is compared to the long hydrocarbon chains. ©2020 McGraw-Hill Education. 4  Triacylglycerols (triglycerides) Simple triacylglycerols are composed of three identical fatty acid side chains, whereas mixed triacylglycerols have two or three different fatty acids. ©2020 McGraw-Hill Education. 5  Fatty Acids in Triacylglycerois ©2020 McGraw-Hill Education. 6  Features of Fatty Acids All fatty acid chains are unbranched, but they must be saturated or unsaturated. Naturally occurring fatty acids have an even number of carbon atoms. All double bonds in naturally occurring fatty acids have the Z configuration. The melting point of a fatty acid depends on the degree of unsaturation. The most common saturated fatty acids are palmitic and stearic acid. The most common unsaturated fatty acid is oleic acid. Linoleic and linolenic acids are called essential fatty acids because we cannot synthesize them and must acquire them from our diets. ©2020 McGraw-Hill Education. 7  Fats vs. Oils Both fats and oils are triesters of glycerol and fatty acids. Fats have higher melting points, making them solids at room temperature. Oils have lower melting points, making them liquids at room temperature. The melting point difference between fats and oils correlates with the number of degrees of unsaturation present in the fatty acid side chain. As the number of double bonds increases, the melting point decreases, as it does for the constituent fatty acids as well. Solid fats have a relatively high percentage of saturated fatty acids and are generally of animal origin. Liquid oils have a higher percentage of unsaturated fatty acids and are generally of vegetable origin. ©2020 McGraw-Hill Education. 8  3D Structures of Triacylglycerols Fish oils, such as cod liver and herring oils, are very rich in polyunsaturated triacylglycerols. These triacylglycerols pack so poorly that they have very low melting points—they remain liquids even in the cold water inhabited by these fish. ©2020 McGraw-Hill Education. 9  Fatty Acid Composition of some Fats and Oils Table 29.3 Fatty Acid Composition of Some Fats and Oils Source %Saturated fatty acids %Oleic acid %Linoleic acid beef 49-62 37-43 2-3 Milk 37 33 3 coconut 86 7 − corn 11-16 19-49 34-62 olive 11 84 4 palm 43 40 8 safflower 9 13 78 soybean 15 20 52 Unsaturated Data from Merck Index, 10th ed. Rahway, NJ: Merck and Co.; and Wilson, et al., 1967,Principles of Nutrition,2nd ed. New York: Wiley. ©2020 McGraw-Hill Education. 10  Hydrolysis of Triacylglycerols You are already familiar with hydrolysis, hydrogenation and oxidation, reactions that triacylglycerols undergo. ©2020 McGraw-Hill Education. 11  Hydrogenation and Oxidation ©2020 McGraw-Hill Education. 12  Energy Storage in Lipids In the cell, the principal function of triacylglycerols is energy storage. Complete oxidation of a triacylglycerol yields CO2, H2O, and a great deal of energy. ©2020 McGraw-Hill Education. 13  Phospholipids Phospholipids are hydrolyzable lipids that contain a phosphorus atom. There are two common types of phospholipids—phosphoacylglycerols and sphingomyelins. Both classes are found almost exclusively in the cell membranes of plants and animals. Phospholipids are organic derivatives of phosphoric acid, formed by replacing two of the H atoms by R groups. This type of functional group is called a phosphodiester, or a phosphoric acid diester. In cells, the remaining OH group on phosphorus loses its proton, giving the phosphodiester a net negative charge. ©2020 McGraw-Hill Education. 14  Phosphoacylglycerols Phosphoacylglycerols (phosphoglycerides) are the second most abundant type of lipid. They form the principal lipid component of most cell membranes. Their structure resembles that of triacylglycerols except that in phosphoacylglycerols, only two of the hydroxy groups of glycerol are esterified with fatty acids. The third OH group is part of a phosphodiester, which is also bonded to a low molecular weight alcohol. ©2020 McGraw-Hill Education. 15  Types of Phosphoacylglycerols There are two prominent types of phosphoacylglycerols which differ in the identity of the R″ group in the phosphodiester. 1. When R′′ = CH2CH2NH3+, the compound is called a phosphatidylethanolamine or cephalin. 2. When R′′ = CH2CH2N(CH3)3+, the compound is called a phosphatidylcholine or lecithin. The middle carbon of the glycerol backbone of all these compounds is a stereogenic center, usually with the R configuration. ©2020 McGraw-Hill Education. 16  Lipid Bilayers The two fatty acids form two nonpolar “tails” that lie parallel to each other, while the phosphodiester end of the molecule is a charged or polar “head.” When these phospholipids are mixed with water, they assemble in an arrangement called a lipid bilayer. The ionic heads are oriented on the outside and the nonpolar tails on the inside. When the fatty acids are saturated, they pack well in the interior of the lipid bilayer, and the membrane is quite rigid. When there are many unsaturated fatty acids, the nonpolar tails cannot pack as well, and the bilayer is more fluid. Cell membranes are composed of these lipid bilayers. ©2020 McGraw-Hill Education. 17  3D Structure of Phosphoacylglycerols ©2020 McGraw-Hill Education. 18  Sphingomyelins Sphingomyelins are derivatives of the amino alcohol sphingosine, in much the same way that triacylglycerols and phosphoacylglycerols are derivatives of glycerol. Other notable features of sphingomyelin include: A phosphodiester at C1. An amide formed with a fatty acid at C2. The coating that surrounds and insulates nerve cells, the myelin sheath, is particularly rich in sphingomyelins. ©2020 McGraw-Hill Education. 19  Comparison of Lipids ©2020 McGraw-Hill Education. 20  Non-Hydrolyzable lipids Fat Soluble Vitamins Vitamins are organic compounds required in small quantities for normal metabolism. Since our cells cannot synthesize these compounds, they must be obtained in the diet. Vitamins can be categorized as fat soluble or water soluble. The fat soluble vitamins are lipids. Although fat soluble vitamins must be obtained in the diet, they do not have to be consumed every day. Excess vitamins are stored in fat cells, and then used as needed. ©2020 McGraw-Hill Education. 21  Fat Soluble Vitamins (A and D) ©2020 McGraw-Hill Education. 22  Fat Soluble Vitamins (E and K) ©2020 McGraw-Hill Education. 23  Eicosanoids The eicosanoids are a group of potent biologically active compounds containing 20 carbon atoms derived from arachidonic acid. Examples are prostaglandins, leukotrienes, thromboxanes, and prostacyclins. Eicosanoids are local mediators. ©2020 McGraw-Hill Education. 24  Biological Activity of the Eicosanoids Table 29.4 Biological Activity of the Eicosanoids Eicosanoid Effect Eicosanoid Effect Prostaglandins Lower blood pressure Thromboxanes Constrict blood vessels Inhibit blood platelet Trigger blood platelet aggregation aggregation Control inflammation Prostacyclins Dilate blood vessels Lower gastric Inhibit blood platelet secretions aggregation Stimulate ulterine Leukotrienes Constrict smooth contractions muscle, especially in the lungs Relax smooth muscles of uterus ©2020 McGraw-Hill Education. 25  Use of Prostaglandins Because of their wide range of biological functions, prostaglandins and their analogues have found several clinical uses. Dinoprostone, the generic name for PGE2, is administered to relax the smooth muscles of the uterus when labor is induced, and to terminate pregnancies in the early stages. ©2020 McGraw-Hill Education. 26  Prostaglandin Analogs Prostaglandins themselves are unstable in the body, having a half- life of only minutes. Thus, more stable analogues have been developed that retain their biological activity for longer periods. An example is misoprostol, an analogue of PGE1 sold as a mixture of stereoisomers, which is administered to prevent gastric ulcers. ©2020 McGraw-Hill Education. 27  NSAIDs Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) inactivate the cyclooxygenase enzyme (COX) needed for prostaglandin biosynthesis. In this way, NSAIDs block the synthesis of the prostaglandins that cause inflammation (= anti-inflammatory). It was recently discovered that two different cyclooxygenase enzymes, called COX-1 and COX-2 are responsible for prostaglandin synthesis. NSAIDs like aspirin and ibuprofen inactivate both the COX-1 and COX-2 enzymes. This results in an increase in gastric secretions, making an individual more susceptible to ulcer formation. ©2020 McGraw-Hill Education. 28  COX-2 Inhibitors A group of anti-inflammatory drugs that block only the COX-2 enzyme were developed in the 1990’s. These drugs—rofecoxib, valdecoxib, and celecoxib—do not cause an increase in gastric secretions and were thus believed to be especially effective for long-term use in patients with arthritis. Unfortunately, both rofecoxib and valdecoxib have been removed from the market, since their use has been associated with increased risk of heart attack and stroke. ©2020 McGraw-Hill Education. 29  Terpenes Terpenes are lipids composed of repeating five-carbon units called isoprene units. An isoprene unit has five carbons: four in a row, with a one- carbon branch on a middle carbon. Terpenes can be cyclic or acyclic, and may contain heteroatoms. ©2020 McGraw-Hill Education. 30  Identifying Isoprene Units in Terpenes To find an isoprene unit, start at one end of the molecule near a branch point. Then look for a four-carbon chain with a one-carbon branch. This forms one isoprene unit. ©2020 McGraw-Hill Education. 31  Classification of Terpenes Terpenes are classified by the number of isoprene units they contain. A monoterpene contains 10 carbons and has two isoprene units; a sesquiterpene contains 15 carbons and has three isoprene units and so forth. Table 29.5 Classes of Terpenes and Terpenoids Name Number of C atoms Number of isoprene units Monoterpene (Monoterpenoid) 10 2 Sesquiterpene (Sesquiterpenoid) 15 3 Diterpene (Diterpenoid) 20 4 Sesterterpene (Sesterterpenoid) 25 5 Triterpene (triterpenoid) 30 6 Tetraterpene (tetraterpenoid) 40 8 ©2020 McGraw-Hill Education. 32  Examples of Common Terpenes Figure 29.8 ©2020 McGraw-Hill Education. 33  Terpene Biosynthesis The high efficiency of the biosynthesis of terpenes is accomplished because: The same reaction is used over and over again to prepare progressively more complex compounds. Key intermediates along the way serve as the starting materials for a wide variety of other compounds. All terpenes are synthesized from dimethylallyl diphosphate and isopentenyl diphosphate. Organic diphosphates (R-OPP) contain a good leaving group (diphosphate) ©2020 McGraw-Hill Education. 34  Terpene Biosynthesis-1 The overall strategy for terpene biosynthesis from dimethylallyl pyrophosphate and isopentenyl pyrophosphate is summarized below. Figure 29.9 ©2020 McGraw-Hill Education. 35  Terpene Biosynthesis Mechanisms Both SN1 and E1 processes are involved in terpene formation. ©2020 McGraw-Hill Education. 36  Steroids Steroids are a group of tetracyclic lipids, many of which have biological activity. Steroids are composed of three six-membered rings and one five- membered ring, that are joined together as drawn. Many steroids also have methyl groups located at the two-ring junctions as shown called angular methyl groups. The steroid rings are lettered A, B, C, and D, and the 17 ring carbons are numbered as shown. The two angular methyl groups are numbered C18 and C19. ©2020 McGraw-Hill Education. 37  Cis- and Trans- Fused Rings Whenever two rings are fused together, the substituents at the ring fusion can be arranged cis or trans. Consider decalin, which consists of two six-membered rings fused together. 3D structures show how different these two possible arrangements actually are. The two rings of trans-decalin lie roughly in the same plane. The two rings of cis-decalin are almost perpendicular to each other. The trans arrangement is lower in energy, and therefore more stable. ©2020 McGraw-Hill Education. 38  3D Structure of Steroids In steroids, the most common arrangement by far is the all trans. Because of this, all four rings in the steroid skeleton lie in the same plane, and the ring system is fairly rigid. The two angular methyl groups are oriented perpendicular to the plane of the molecule. Figure 29.10 ©2020 McGraw-Hill Education. 39  Cholesterol Cholesterol has eight stereogenic carbons, so there are 28 = 256 possible stereoisomers. In nature, however, only the following stereoisomer exists: Cholesterol is essential to life because it forms an important component to cell membranes and is the starting material for all other steroids. Humans do not have to ingest cholesterol because it is synthesized in the liver and then transported to other tissues. Cholesterol is synthesized in the body from squalene (C30). ©2020 McGraw-Hill Education. 40  Cholesterol-Lowering Drugs Several drugs are now available to reduce the level of cholesterol in the bloodstream. These compounds act by blocking the biosynthesis of cholesterol in its early stages. Two examples are atorvastatin (Lipitor) and simvastatin (Zocor). Figure 29.12 ©2020 McGraw-Hill Education. 41  Steroidal Sex Hormones ©2020 McGraw-Hill Education. 42  Synthetic Hormone Steroids Synthetic analogues of these steroids have found important uses, such as in oral contraceptives. Synthetic androgen analogues, called anabolic steroids, promote muscle growth. Although they are used by athletes, their use is not permitted in competitive sports. ©2020 McGraw-Hill Education. 43  Adrenal Cortical Steroids A second group of steroid hormones includes the adrenal cortical steroids. Examples are cortisone, cortisol, and aldosterone. All of these compounds are synthesized in the outer layer of the adrenal gland. Cortisone and cortisol serve as anti-inflammatory agents and they also regulate carbohydrate metabolism. Aldosterone regulates blood pressure and volume by controlling the concentration of Na+ and K+ in body fluids. ©2020 McGraw-Hill Education. 44