88 CHAPTER 26 LIPIDS ipids differ from the other classes of naturally occurring biomolecules(carbohy drates, proteins, and nucleic acids) in that they are more soluble in non-to-weakly polar solvents(diethyl ether, hexane, dichloromethane) than they are in water. They include a variety of structural types, a collection of which is introduced in this chapter. heti o n spite of the number of different structural types, lipids share a common biosyn- bohydrate metabolism, called glycolysis, glucose is converted to lactic acid. Pyruvic acid C6H1206->CH3CCO2H CH3CHCOH Pyruvic acid In most biochemical reactions the pH of the medium is close to 7. At this pH, carboxylic acids are nearly completely converted to their conjugate bases. Thus, it is common practice in biological chemistry to specify the derived carboxylate anion rather than the carboxylic acid itself. For example, we say that glycolysis leads to lactate by way of pyrvate the pyruvate is used by living systems in a number of different ways. One pathway, he leading to lactate and beyond, is concerned with energy storage and production This is not the only pathway available to pyruvate, however. A significant fraction of it is converted to acetate for use as a starting material in the biosynthesis of more com- plex substances, especially lipids. By far the major source of lipids is biosynthesis via acetate and this chapter is organized around that theme. We'll begin by looking at the reaction in which acetate(two carbons) is formed from pyruvate(three carbons). 1015 Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
1015 CHAPTER 26 LIPIDS L ipids differ from the other classes of naturally occurring biomolecules (carbohydrates, proteins, and nucleic acids) in that they are more soluble in non-to-weakly polar solvents (diethyl ether, hexane, dichloromethane) than they are in water. They include a variety of structural types, a collection of which is introduced in this chapter. In spite of the number of different structural types, lipids share a common biosynthetic origin in that they are ultimately derived from glucose. During one stage of carbohydrate metabolism, called glycolysis, glucose is converted to lactic acid. Pyruvic acid is an intermediate. In most biochemical reactions the pH of the medium is close to 7. At this pH, carboxylic acids are nearly completely converted to their conjugate bases. Thus, it is common practice in biological chemistry to specify the derived carboxylate anion rather than the carboxylic acid itself. For example, we say that glycolysis leads to lactate by way of pyruvate. Pyruvate is used by living systems in a number of different ways. One pathway, the one leading to lactate and beyond, is concerned with energy storage and production. This is not the only pathway available to pyruvate, however. A significant fraction of it is converted to acetate for use as a starting material in the biosynthesis of more complex substances, especially lipids. By far the major source of lipids is biosynthesis via acetate and this chapter is organized around that theme. We’ll begin by looking at the reaction in which acetate (two carbons) is formed from pyruvate (three carbons). C6H12O6 Glucose O CH3CCO2H Pyruvic acid OH CH3CHCO2H Lactic acid Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
1016 CHAPTER TWENTY-SIX Lipids 26.1 ACETYL COENZYME A The form in which acetate is used in most of its important biochemical reactions is acetyl coenzyme A(Figure 26.la). Acetyl coenzyme A is a thioester(Section 20.12). Its for mation from pyruvate involves several steps and is summarized in the overall equation CH3CCOH+ CoASH NAD-CH3 CSCoA NADH CO2 t H Oxidized Acetyl Reduced Carbon Proton form of dioxide nicotinamide dinucleotide dinucleotide Coenzyme A was isolated All the individual steps are catalyzed by enzymes. NAD(Section 15.11)is required as an oxidizing agent, and coenzyme A(Figure 26 1b) is the acetyl group acceptor. Coen- hemist Lipmann shared the zyme A is a thiol; its chain terminates in a sulfhydryl(--SH) group. Acetylation of the mann, an American bio- 953 Nobel Prize in physiol- sulthydryl group of coenzyme A gives acetyl coenzyme A ogy or medicine for this As we saw in Chapter 20, thioesters are more reactive than ordinary esters toward nucleophilic acyl substitution. They also contain a greater proportion of enol at equilib- rium. Both properties are apparent in the properties of acetyl coenzyme A. In some reac tions it is the carbonyl group of acetyl coenzyme a that reacts; in others it is the a carbon atom O CH3CSCOA CHa=CSCOA cetyl coenzyme A Enol form nucleophilic reaction at substitution HY: CH3C-Y:+ HSCoA E-CHCSCoA H HO OQ OH OH H Ho-P-0tooVon O NH, FIGURE 26.1 Structures of (a)R=CCH, Acetyl coenzyme A(abbreviation: CH, CSCoA (a)acetyl coenzyme a and R=H Coenzyme A(abbreviation: CoASH) (b)coenzyme A Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
1016 CHAPTER TWENTY-SIX Lipids 26.1 ACETYL COENZYME A The form in which acetate is used in most of its important biochemical reactions is acetyl coenzyme A (Figure 26.1a). Acetyl coenzyme A is a thioester (Section 20.12). Its formation from pyruvate involves several steps and is summarized in the overall equation: All the individual steps are catalyzed by enzymes. NAD (Section 15.11) is required as an oxidizing agent, and coenzyme A (Figure 26.1b) is the acetyl group acceptor. Coenzyme A is a thiol; its chain terminates in a sulfhydryl (±SH) group. Acetylation of the sulfhydryl group of coenzyme A gives acetyl coenzyme A. As we saw in Chapter 20, thioesters are more reactive than ordinary esters toward nucleophilic acyl substitution. They also contain a greater proportion of enol at equilibrium. Both properties are apparent in the properties of acetyl coenzyme A. In some reactions it is the carbonyl group of acetyl coenzyme A that reacts; in others it is the - carbon atom. O CH3CSCoA Acetyl coenzyme A CH2 OH CSCoA Enol form reaction at carbon nucleophilic acyl substitution HY E E O CH2CSCoA H Y O CH3C HSCoA OO CH3CCOH Pyruvic acid O CH3CSCoA Acetyl coenzyme A CoASH Coenzyme A NAD Oxidized form of nicotinamide adenine dinucleotide NADH Reduced form of nicotinamide adenine dinucleotide CO2 Carbon dioxide H Proton HO P O HO SR CH3 NH2 O N N N N O N O N H H OH O O O P P HO OH O O CH3 O HO (a) (b) Acetyl coenzyme A (abbreviation: CH 3 O R H Coenzyme A (abbreviation: CoASH) R CCH O CSCoA) 3 Coenzyme A was isolated and identified by Fritz Lipmann, an American biochemist. Lipmann shared the 1953 Nobel Prize in physiology or medicine for this work. FIGURE 26.1 Structures of (a) acetyl coenzyme A and (b) coenzyme A. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
ee We'll see numerous examples of both reaction types in the following Keep in mind that in vivo reactions (reactions in living systems) are enzyme-ca nd occur at rates that are far greater than when the same transformations are ca in vitro ("in glass") in the absence of enzymes. In spite of the rapidity with which enzyme-catalyzed reactions take place, the nature of these transformations is essentiall the same as the fundamental processes of organic chemistry described throughout this text Fats are one type of lipid. They have a number of functions in living systems, luding that of energy storage. Although carbohydrates serve as a source of readily more efficient for an organism to store energy in the form of fat because it requireS Rr available energy, an equal weight of fat delivers over twice the amount of energy. It mass than storing the same amount of energy in carbohydrates or proteins. How living systems convert acetate to fats is an exceedingly complex story, one that is well understood in broad outline and becoming increasingly clear in detail as well We will examine several aspects of this topic in the next few sections, focusing mostly on its structural and chemical features 26.2 FATS, OILS, AND FATTY ACIDS Fats and oils are naturally occurring mixtures of triacylglycerols, also called triglyc- An experiment describing generaly ignore this distinction and refer to both groups as lie d oils are liquids. We the analysis of the trioeral brides. They differ in that fats are solids at room temperature Triacylglycerols are built on a glycerol framework vegetable oils is described in the May 1988 issue of the ournal of chemical educa. on(pp.464-466) HOCH, CHCH,OH RCOCHCHCH,OCR OCR Glycerol A triacylglycerol All three acyl groups in a triacylglycerol may be the same, all three may be different or one may be different from the other two Figure 26.2 shows the structures of two typical triacylglycerols, 2-oleyl-1, 3 distearylglycerol(Figure 26. 2a) and tristearin(Figure 26.2b). Both occur naturally--in cocoa butter, for example. All three acyl groups in tristearin are stearyl(octadecanoyl) groups. In 2-oleyl-1, 3-distearylglycerol, two of the acyl groups are stearyl, but the one in the middle is oleyl(cis-9-octadecenoyl). As the figure shows, tristearin can be pre pared by catalytic hydrogenation of the carbon-carbon double bond of 2-oleyl-1, 3 distearylglycerol. Hydrogenation raises the melting point from 43C in 2-oleyl-1, 3 distearylglycerol to 72C in tristearin and is a standard technique in the food industry for converting liquid vegetable oils to solid"shortenings. "The space-filling models of Strictly speaking, the te the two show the flatter structure of tristearin, which allows it to pack better in a crys se carboxylic acids that tal lattice than the more irregular shape of 2-oleyl-1, 3-distearylglycerol permits. This ur naturally in triacylglyc. irregular shape is a direct result of the cis double bond in the side chain. erols. Many chemists and Hydrolysis of fats yields glycerol and long-chain fatty acids. Thus, tristearin gives to all unbranched carboxylic glycerol and three molecules of stearic acid on hydrolysis. Table 26.1 lists a few repre- acids, irrespective of their sentative fatty acids. As these examples indicate, most naturally occurring fatty acids possess an even number of carbon atoms and an unbranched carbon chain. The carbon fatty acids. Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
26.2 Fats, Oils, and Fatty Acids 1017 We’ll see numerous examples of both reaction types in the following sections. Keep in mind that in vivo reactions (reactions in living systems) are enzyme-catalyzed and occur at rates that are far greater than when the same transformations are carried out in vitro (“in glass”) in the absence of enzymes. In spite of the rapidity with which enzyme-catalyzed reactions take place, the nature of these transformations is essentially the same as the fundamental processes of organic chemistry described throughout this text. Fats are one type of lipid. They have a number of functions in living systems, including that of energy storage. Although carbohydrates serve as a source of readily available energy, an equal weight of fat delivers over twice the amount of energy. It is more efficient for an organism to store energy in the form of fat because it requires less mass than storing the same amount of energy in carbohydrates or proteins. How living systems convert acetate to fats is an exceedingly complex story, one that is well understood in broad outline and becoming increasingly clear in detail as well. We will examine several aspects of this topic in the next few sections, focusing mostly on its structural and chemical features. 26.2 FATS, OILS, AND FATTY ACIDS Fats and oils are naturally occurring mixtures of triacylglycerols, also called triglycerides. They differ in that fats are solids at room temperature and oils are liquids. We generally ignore this distinction and refer to both groups as fats. Triacylglycerols are built on a glycerol framework. All three acyl groups in a triacylglycerol may be the same, all three may be different, or one may be different from the other two. Figure 26.2 shows the structures of two typical triacylglycerols, 2-oleyl-1,3- distearylglycerol (Figure 26.2a) and tristearin (Figure 26.2b). Both occur naturally—in cocoa butter, for example. All three acyl groups in tristearin are stearyl (octadecanoyl) groups. In 2-oleyl-1,3-distearylglycerol, two of the acyl groups are stearyl, but the one in the middle is oleyl (cis-9-octadecenoyl). As the figure shows, tristearin can be prepared by catalytic hydrogenation of the carbon–carbon double bond of 2-oleyl-1,3- distearylglycerol. Hydrogenation raises the melting point from 43°C in 2-oleyl-1,3- distearylglycerol to 72°C in tristearin and is a standard technique in the food industry for converting liquid vegetable oils to solid “shortenings.” The space-filling models of the two show the flatter structure of tristearin, which allows it to pack better in a crystal lattice than the more irregular shape of 2-oleyl-1,3-distearylglycerol permits. This irregular shape is a direct result of the cis double bond in the side chain. Hydrolysis of fats yields glycerol and long-chain fatty acids. Thus, tristearin gives glycerol and three molecules of stearic acid on hydrolysis. Table 26.1 lists a few representative fatty acids. As these examples indicate, most naturally occurring fatty acids possess an even number of carbon atoms and an unbranched carbon chain. The carbon HOCH2CHCH2OH OH Glycerol OCR RCOCH2CHCH2OCR O O O A triacylglycerol An experiment describing the analysis of the triglyceride composition of several vegetable oils is described in the May 1988 issue of the Journal of Chemical Education (pp. 464–466). Strictly speaking, the term “fatty acid” is restricted to those carboxylic acids that occur naturally in triacylglycerols. Many chemists and biochemists, however, refer to all unbranched carboxylic acids, irrespective of their origin and chain length, as fatty acids. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
1018 CHAPTER TWENTY-SIX Lipids OC(CH2)16CH OC(CH,)16CH H,C H, HC-OC(CH2)6CH2 CH(CH2)CH HC-OC(CH2)1CI OC(CH2)16CH3 H OC(CH2)16CH3 2-Oleyl-1, 3-distearylglycerol(mp 43C Tristearin(mp72°C) FIGURE 26. 2 The structures of two typical triacylglycerols. (a)2-oleyl-1, 3-distearylglycerol is a naturally occurring triacyl- glycerol found in cocoa butter. The cis double bond of its oleyl group gives the molecule a shape that interferes with efficient crys tal packing. (b)Catalytic hydrogenation converts 2-oleyl-1, 3-distearylglycerol to tristearin Tristearin has a higher melting point than 2-oleyl-1, 3-distearylglycerol TABLE 26.1 Some Representative Fatty Acids Structural formula Systematic name Common name Saturated fatty acids CH3(CH2)10COOH Dodecanoic acid acid CH3(CH2)12 COOH Tetradecanoic acid Myristic acid CH3(CH2)14CO0H Hexadecanoic acid Palmitic acid CH3(CH2)16COOH Octadecanoic acid Stearic acid CH3(CH2)18COOH Icosanoic acid Arachidic acid Unsaturated fatty acids CH3(CH2)7CH=CH(CH2)7COOH (Z)-9-Octadecenoic acid oleic acid CH3(CH2)4CH=CHCH, CH=CH(CH2),COOH (9z122)-912 Octadecadienoic acid CHa CH2 CH=CHCH2 CH=CHCH2 CH=CH( CH2)7COOH (9z122152)-9,12,15 Linolenic acid ctadecatrienoic acid CH3(CH2)4CH=CHCH2 CH=CHCH2 CH=CHCH2 CH=CH(CH2)3COOH (5Z, 8Z, 11Z, 14Z) Arachidonic acid 58,11,14 Icosatetraenoic acid Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
1018 CHAPTER TWENTY-SIX Lipids H2C CœC H2C OC(CH2)16CH3 OC(CH2)16CH3 H2C ± ± ± ± HC±OC(CH2)6CH2 CH2(CH2)6CH3 H2, Pt ± ± ± ± H H 2-Oleyl-1,3-distearylglycerol (mp 43°C) Tristearin (mp 72°C) O O O O O O OC(CH2)16CH3 OC(CH2)16CH3 H2C ± ± ± ± HC±OC(CH2)16CH3 O O O O O O ¢± (a) (b) FIGURE 26.2 The structures of two typical triacylglycerols. (a) 2-Oleyl-1,3-distearylglycerol is a naturally occurring triacylglycerol found in cocoa butter. The cis double bond of its oleyl group gives the molecule a shape that interferes with efficient crystal packing. (b) Catalytic hydrogenation converts 2-oleyl-1,3-distearylglycerol to tristearin. Tristearin has a higher melting point than 2-oleyl-1,3-distearylglycerol. TABLE 26.1 Some Representative Fatty Acids Systematic name Dodecanoic acid Tetradecanoic acid Hexadecanoic acid Octadecanoic acid Icosanoic acid (Z)-9-Octadecenoic acid (9Z,12Z)-9,12- Octadecadienoic acid (9Z,12Z,15Z)-9,12,15- Octadecatrienoic acid (5Z,8Z,11Z,14Z)- 5,8,11,14- Icosatetraenoic acid Common name Lauric acid Myristic acid Palmitic acid Stearic acid Arachidic acid Oleic acid Linoleic acid Linolenic acid Arachidonic acid Structural formula Saturated fatty acids CH3(CH2)10COOH CH3(CH2)12COOH CH3(CH2)14COOH CH3(CH2)16COOH CH3(CH2)18COOH Unsaturated fatty acids CH3(CH2)7CHœCH(CH2)7COOH CH3(CH2)4CHœCHCH2CHœCH(CH2)7COOH CH3CH2CHœCHCH2CHœCHCH2CHœCH(CH2)7COOH CH3(CH2)4CHœCHCH2CHœCHCH2CHœCHCH2CHœCH(CH2)3COOH Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
26.3 Fatty Acid Biosynthesis 1019 in may be saturated or it can contain one or more double bonds. When double present, they are almost always cis. Acyl groups containing 14-20 carbon ate ter of glycerol, the fat substi- he most abundant in triacylglycerols PROBLEM 26. 1 What fatty acids are produced on hydrolysis of 2-oleyl-1, 3 esters of sucrose in which the yl groups are derived from distearylglycerol? What other triacylglycerol gives the same fatty acids and in thefatty acidsOlestra has many same proportions as 2-oleyl-1, 3-distearylglycerol? of the physical and taste the major source of trans fats comes from the processing of natural fats and oils. In the For more about olestra, see course of hydrogenating some of the double bonds in a triacylglycerol, stereoisomeriza- Journal of chemical educa. tion can occur, converting cis double bonds to trans. Furthermore, the same catalysts that tion, pp370-372 promote hydrogenation promote the reverse process--dehydrogenation-by which new double bonds, usually trans, are introduced in the acyl group Fatty acids occur naturally in forms other than as glyceryl triesters, and we'll see numerous examples as we go through the chapter. One recently discovered fatty acid the Journal of Chemical Edu. derivative is anandamide tains an article entitled Trans Fatty Acids. Anandamide Anandamide is an ethanolamine(h,NCH, Ch,oh) amide of arachidonic acid(see table 26.1). It was isolated from pigs brain in 1992 and identified as the substance that nor- mally binds to the cannabinoid receptor. "The active component of marijuana, entists had long wondered what compound in the body was the natural substrate binding site. Anandamide is that compound, and it is now probably more appropriate to Other than that both are speak of cannabinoids binding to the anandamide receptor instead of vice versa. Anan- lipids, there are no obvious damide seems to be involved in moderating pain. Once the identity of the"endogenous structural similarities be. cannabinoid"was known, scientists looked specifically for it and found it in some sur- prising places--chocolate, for example Fatty acids are biosynthesized by way of acetyl coenzyme A. The following sec- tion outlines the mechanism of fatty acid biosynthesis 26.3 FATTY ACID BIOSYNTHESIS We can describe the major elements of fatty acid biosynthesis by considering the for- mation of butanoic acid from two molecules of acetyl coenzyme A. The"machinery responsible for accomplishing this conversion is a complex of enzymes known as fatty acid synthetase. Certain portions of this complex, referred to as acyl carrier protein (ACP), bear a side chain that is structurally similar to coenzyme A. An important early step in fatty acid biosynthesis is the transfer of the acetyl group from a molecule of acetyl coenzyme A to the sulfhydryl group of acyl carrier protein. CH3 CSCOA+HS一ACP—>CH3CS-ACP+ HSCOA S-Acetyl acyl Coenzyme a A Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
26.3 Fatty Acid Biosynthesis 1019 chain may be saturated or it can contain one or more double bonds. When double bonds are present, they are almost always cis. Acyl groups containing 14–20 carbon atoms are the most abundant in triacylglycerols. PROBLEM 26.1 What fatty acids are produced on hydrolysis of 2-oleyl-1,3- distearylglycerol? What other triacylglycerol gives the same fatty acids and in the same proportions as 2-oleyl-1,3-distearylglycerol? A few fatty acids with trans double bonds (trans fatty acids) occur naturally, but the major source of trans fats comes from the processing of natural fats and oils. In the course of hydrogenating some of the double bonds in a triacylglycerol, stereoisomerization can occur, converting cis double bonds to trans. Furthermore, the same catalysts that promote hydrogenation promote the reverse process—dehydrogenation—by which new double bonds, usually trans, are introduced in the acyl group. Fatty acids occur naturally in forms other than as glyceryl triesters, and we’ll see numerous examples as we go through the chapter. One recently discovered fatty acid derivative is anandamide. Anandamide is an ethanolamine (H2NCH2CH2OH) amide of arachidonic acid (see Table 26.1). It was isolated from pig’s brain in 1992 and identified as the substance that normally binds to the “cannabinoid receptor.” The active component of marijuana, 9 -tetrahydrocannabinol (THC), must exert its effect by binding to a receptor, and scientists had long wondered what compound in the body was the natural substrate for this binding site. Anandamide is that compound, and it is now probably more appropriate to speak of cannabinoids binding to the anandamide receptor instead of vice versa. Anandamide seems to be involved in moderating pain. Once the identity of the “endogenous cannabinoid” was known, scientists looked specifically for it and found it in some surprising places—chocolate, for example. Fatty acids are biosynthesized by way of acetyl coenzyme A. The following section outlines the mechanism of fatty acid biosynthesis. 26.3 FATTY ACID BIOSYNTHESIS We can describe the major elements of fatty acid biosynthesis by considering the formation of butanoic acid from two molecules of acetyl coenzyme A. The “machinery” responsible for accomplishing this conversion is a complex of enzymes known as fatty acid synthetase. Certain portions of this complex, referred to as acyl carrier protein (ACP), bear a side chain that is structurally similar to coenzyme A. An important early step in fatty acid biosynthesis is the transfer of the acetyl group from a molecule of acetyl coenzyme A to the sulfhydryl group of acyl carrier protein. O CH3CSCoA Acetyl coenzyme A O CH3CS ACP S-Acetyl acyl carrier protein HSCoA Coenzyme A HS ACP Acyl carrier protein N H OH O Anandamide Instead of being a triacyl ester of glycerol, the fat substitute olestra is a mixture of hexa-, hepta-, and octaacyl esters of sucrose in which the acyl groups are derived from fatty acids. Olestra has many of the physical and taste properties of a fat but is not metabolized by the body and contributes no calories. For more about olestra, see the April 1997 issue of the Journal of Chemical Education, pp. 370–372. The September 1997 issue of the Journal of Chemical Education (pp. 1030–1032) contains an article entitled “Trans Fatty Acids.” Other than that both are lipids, there are no obvious structural similarities between anandamide and THC. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website