《有机化学》课程教学资源（教材文献，英文版）CHAPTER 26 LIPIDS

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 (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. In spite of the number of different structural types, lipids share a common biosyn￾thetic origin in that they are ultimately derived from glucose. During one stage of car￾bohydrate 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 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). 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 for￾mation 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. Coen￾zyme 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 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 - 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 Lip￾mann, an American bio￾chemist. Lipmann shared the 1953 Nobel Prize in physiol￾ogy 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 triglyc￾erides. 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 pre￾pared 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 crys￾tal 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 repre￾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 HOCH2CHCH2OH OH Glycerol OCR RCOCH2CHCH2OCR O O O A triacylglycerol An experiment describing the analysis of the triglyc￾eride composition of several vegetable oils is described in the May 1988 issue of the Journal of Chemical Educa￾tion (pp. 464–466). Strictly speaking, the term “fatty acid” is restricted to those carboxylic acids that occur naturally in triacylglyc￾erols. 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 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 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, stereoisomeriza￾tion 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 nor￾mally binds to the “cannabinoid receptor.” The active component of marijuana, 9 -tetrahydrocannabinol (THC), must exert its effect by binding to a receptor, and sci￾entists 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. Anan￾damide 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 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. 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 es￾ter of glycerol, the fat substi￾tute 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 Educa￾tion, pp. 370–372. The September 1997 issue of the Journal of Chemical Edu￾cation (pp. 1030–1032) con￾tains an article entitled “Trans Fatty Acids.” Other than that both are lipids, there are no obvious structural similarities be￾tween anandamide and THC. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website

1020 CHAPTER TWENTY-SIX Lipids PROBLEM 26.2 Using HSCoA and Hs-ACP as abbreviations for coenzyme a and acyl carrier protein, respectively, write a structural formula for the tetrahedral intermediate in the preceding reaction A second molecule of acetyl coenzyme A reacts with carbon dioxide(actually bicarbonate ion at biological pH) to give malonyl coenzyme A CH3 CSCoA HCO3 OCCH, CSCoA HO Malony Water coenzyme A coenzyme A Formation of malonyl coenzyme A is followed by a nucleophilic acyl substitution, which transfers the malonyl group to the acyl carrier protein as a thioester. OCCHCSCOA+HS一ACP OCCHCS-ACP+ HSCOA Acyl carrier S-Malonyl acyl When both building block units are in place on the acyl carrier protein, carbon-car- bon bond formation occurs between the a-carbon atom of the malonyl group and the carbonyl carbon of the acetyl group. This is shown in step I of Figure 26.3. Carbon-car- bon bond formation is accompanied by decarboxylation and produces a four-carbon ace- toacetyl (3-oxobutanoyl) group bound to acyl carrier protein. The acetoacetyl group is then transformed to a butanoyl group by the reaction equence illustrated in steps 2 to 4 of Figure 26.3. The four carbon atoms of the butanoyl group originate in two molecules of acetyl coenzyme A. Carbon dioxide assists the reaction but is not incorporated into the prod uct. The same carbon dioxide that is used to convert one molecule of acetyl coenzyme A to malonyl coenzyme A is regenerated in the decarboxylation step that accompanies carbon-carbon bond formation Successive repetitions of the steps shown in Figure 26.3 give unbranched acyl groups having 6, 8, 10, 12, 14, and 16 carbon atoms. In each case, chain extension occurs by reaction with a malonyl group bound to the acyl carrier protein. Thus, the biosyn- thesis of the 16-carbon acyl group of hexadecanoic (palmitic) acid can be represented by the overall equation oO CH3CS-ACP 7HOCCH, CS-ACP+ 14 NADPH 14 H3o S-Malonyl acyl Reduced form Hydronium carner protein carrier protein of coenzyme CH3(CH2)14CS-ACP+ 7C0,+ 7HS-ACP+ 14 NADP 21 H,O S-Hexadecanoyl acyl Carbon Acyl carrier Oxidized form Water dioxide of Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

1020 CHAPTER TWENTY-SIX Lipids PROBLEM 26.2 Using HSCoA and HS±ACP as abbreviations for coenzyme A and acyl carrier protein, respectively, write a structural formula for the tetrahedral intermediate in the preceding reaction. A second molecule of acetyl coenzyme A reacts with carbon dioxide (actually bicarbonate ion at biological pH) to give malonyl coenzyme A: Formation of malonyl coenzyme A is followed by a nucleophilic acyl substitution, which transfers the malonyl group to the acyl carrier protein as a thioester. When both building block units are in place on the acyl carrier protein, carbon–car￾bon bond formation occurs between the -carbon atom of the malonyl group and the carbonyl carbon of the acetyl group. This is shown in step 1 of Figure 26.3. Carbon–car￾bon bond formation is accompanied by decarboxylation and produces a four-carbon ace￾toacetyl (3-oxobutanoyl) group bound to acyl carrier protein. The acetoacetyl group is then transformed to a butanoyl group by the reaction sequence illustrated in steps 2 to 4 of Figure 26.3. The four carbon atoms of the butanoyl group originate in two molecules of acetyl coenzyme A. Carbon dioxide assists the reaction but is not incorporated into the prod￾uct. The same carbon dioxide that is used to convert one molecule of acetyl coenzyme A to malonyl coenzyme A is regenerated in the decarboxylation step that accompanies carbon–carbon bond formation. Successive repetitions of the steps shown in Figure 26.3 give unbranched acyl groups having 6, 8, 10, 12, 14, and 16 carbon atoms. In each case, chain extension occurs by reaction with a malonyl group bound to the acyl carrier protein. Thus, the biosyn￾thesis of the 16-carbon acyl group of hexadecanoic (palmitic) acid can be represented by the overall equation: 7HS ACP Acyl carrier protein 21 H2O Water 14 NADP Oxidized form of coenzyme 7CO2 Carbon dioxide S-Hexadecanoyl acyl carrier protein ACP O CH3(CH2)14CS 14 NADPH Reduced form of coenzyme 14 H3O Hydronium ion S-Acetyl acyl carrier protein ACP O CH3CS S-Malonyl acyl carrier protein ACP O 7HOCCH2CS O HS ACP Acyl carrier protein O O OCCH2CSCoA Malonyl coenzyme A HSCoA Coenzyme A S-Malonyl acyl carrier protein ACP O O OCCH2CS O CH3CSCoA Acetyl coenzyme A O O OCCH2CSCoA Malonyl coenzyme A H2O Water HCO3  Bicarbonate Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website

26.3 Fatty Acid Biosynthesis 1021 Step 1: An acetyl group is transferred to the a carbon atom of the malonyl group with evolution of carbon dioxide. Presumably decarboxylation gives an enol, which attacks the acetyl group ACP -O-C=0 CH C-CH, CS- ACP +-S-ACP C-CH CS-ACP Acetyl and malonyl groups bound to acyl acyl carrier Step 2: The ketone carbonyl of the acetoacetyl group is reduced to an alcohol function. This reduction requires NADPH as a coenzyme (NADPH is the phosphate ester of NADh and reacts similarly to it. CH CCH CS-ACP NADPh+ HO+ CH,CHCH,CS-ACP NADP+ H,O Reduced Hydronium Oxidized form of acyl carrier protein form of coenzyme Step 3: Dehydration of the B-hydroxy acyl group CH CHCH CS-ACP CHCH=CHCS一ACP+H2O S-ci carey brtateiy acyl carrier protein Step 4: Reduction of the double bond of the a, B-unsaturated acyl group. This step requires NADPH as a coenzyme CH ACP NADPH HO+ > CH CH-CH CS -ACP+ NADP++ Ho S-2-Butenoyl Reduced Hydronium S-Butanoyl Oxidized coenzym 26.3 Mechanism of PROBLEM 26.3 By analogy to the intermediates given in steps 1-4 of Figure hesis of a butanoyl 26.3, write the sequence of acyl groups that are attached to the acyl carrier pro- rom acetyl and mal tein in the conversion of onyl building blocks CH3(CH2)12CS-ACP to CH3(CH2)14CS-ACP Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

26.3 Fatty Acid Biosynthesis 1021 PROBLEM 26.3 By analogy to the intermediates given in steps 1–4 of Figure 26.3, write the sequence of acyl groups that are attached to the acyl carrier pro￾tein in the conversion of CH3(CH2)12CS±ACP to O X CH3(CH2)14CS±ACP O X Step 1: An acetyl group is transferred to the carbon atom of the malonyl group with evolution of carbon dioxide. Presumably decarboxylation gives an enol, which attacks the acetyl group. Step 2: The ketone carbonyl of the acetoacetyl group is reduced to an alcohol function. This reduction requires NADPH as a coenzyme. (NADPH is the phosphate ester of NADH and reacts similarly to it.) CH3C O S ACP O O C CH2CS O ACP Acetyl and malonyl groups bound to acyl carrier protein O C O CH3C O CH2CS O ACP S ACP Carbon dioxide S-Acetoacetyl acyl carrier protein Acyl carrier protein (anionic form) CH3CCH O 2CS O ACP S-Acetoacetyl acyl carrier protein NADPH Reduced form of coenzyme H3O Hydronium ion CH3CHCH2CS O ACP S-3-Hydroxybutanoyl acyl carrier protein NADP Oxidized form of coenzyme H2O Water OH Step 3: Dehydration of the -hydroxy acyl group. CH3CHCH2CS O ACP S-3-Hydroxybutanoyl acyl carrier protein OH CH3CH CHCS O ACP S-2-Butenoyl acyl carrier protein H2O Water Step 4: Reduction of the double bond of the , -unsaturated acyl group. This step requires NADPH as a coenzyme. CH3CH CHCS O ACP S-2-Butenoyl acyl carrier protein NADPH Reduced form of coenzyme H3O Hydronium ion CH3CH CH2CS O ACP S-Butanoyl acyl carrier protein NADP Oxidized form of coenzyme H2O Water 2 FIGURE 26.3 Mechanism of biosynthesis of a butanoyl group from acetyl and mal￾onyl building blocks. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website

CHAPTER TWENTY-SIX Lipids This phase of fatty acid biosynthesis concludes with the transfer of the acyl group from acyl carrier protein to coenzyme A. The resulting acyl coenzyme a molecules car then undergo a number of subsequent biological transformations. One such transforma tion is chain extension, leading to acyl groups with more than 16 carbons. Another is the introduction of one or more carbon-carbon double bonds. A third is acyl transfer from sulfur to oxygen to form esters such as triacylglycerols. The process by which acyl coenzyme A molecules are converted to triacylglycerols involves a type of intermediate alled a phospholipid and is discussed in the following section 26. 4 PHOSPHOLIPIDS Triacylglycerols arise, not by acylation of glycerol itself, but by a sequence of steps in which the first stage is acyl transfer to L-glycerol 3-phosphate(from reduction of dihy droxyacetone 3-phosphate, formed as described in Section 25. 21). The product of this stage is called a phosphatidic acid. CH,OH O o CH,OCR H RCSCoA +R'cSCoa RCO H 2HSCOA CH,,H CH,OPO3H2 Glycer Two acyl coenzyme a molecules Phosphated Coenzyme a 3- (R and r may be the same or they may be different PROBLEM 26.4 What is the absolute configuration(R or S)of L-glycerol 3- phosphate? What must be the absolute configuration of the naturally occurring phosphatidic acids biosynthesized from it? Hydrolysis of the phosphate ester function of the phosphatidic acid gives a diacylglycerol, which then reacts with a third acyl coenzyme A molecule to produce a triacylglycerol O CH,OCR O CH,OCR O CHOCR RCO >RCO R CSCOA H →RCO+H CH,OPO3H2 CHOH CH,OCR Phosphatidic acid Diacylglycerol Triacylglycerol Phosphatidic acids not only are intermediates in the biosynthesis of triacylglycerols but also are biosynthetic precursors of other members of a group of compounds called phosphoglycerides or glycerol phosphatides. Phosphorus-containing derivatives of lipids are known as phospholipids, and phosphoglycerides are one type of phospholipid. nt to prevent One important phospholipid is phosphatidylcholine, also called lecithin. Phos- from sepa- phatidylcholine is a mixture of diesters of phosphoric acid. One ester function is derived from a diacylglycerol, whereas the other is a choline [-OCH2CH2N(CH3)3) unit Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

1022 CHAPTER TWENTY-SIX Lipids This phase of fatty acid biosynthesis concludes with the transfer of the acyl group from acyl carrier protein to coenzyme A. The resulting acyl coenzyme A molecules can then undergo a number of subsequent biological transformations. One such transforma￾tion is chain extension, leading to acyl groups with more than 16 carbons. Another is the introduction of one or more carbon–carbon double bonds. A third is acyl transfer from sulfur to oxygen to form esters such as triacylglycerols. The process by which acyl coenzyme A molecules are converted to triacylglycerols involves a type of intermediate called a phospholipid and is discussed in the following section. 26.4 PHOSPHOLIPIDS Triacylglycerols arise, not by acylation of glycerol itself, but by a sequence of steps in which the first stage is acyl transfer to L-glycerol 3-phosphate (from reduction of dihy￾droxyacetone 3-phosphate, formed as described in Section 25.21). The product of this stage is called a phosphatidic acid. PROBLEM 26.4 What is the absolute configuration (R or S) of L-glycerol 3- phosphate? What must be the absolute configuration of the naturally occurring phosphatidic acids biosynthesized from it? Hydrolysis of the phosphate ester function of the phosphatidic acid gives a diacylglycerol, which then reacts with a third acyl coenzyme A molecule to produce a triacylglycerol. Phosphatidic acids not only are intermediates in the biosynthesis of triacylglycerols but also are biosynthetic precursors of other members of a group of compounds called phosphoglycerides or glycerol phosphatides. Phosphorus-containing derivatives of lipids are known as phospholipids, and phosphoglycerides are one type of phospholipid. One important phospholipid is phosphatidylcholine, also called lecithin. Phos￾phatidylcholine is a mixture of diesters of phosphoric acid. One ester function is derived from a diacylglycerol, whereas the other is a choline unit. [±OCH2CH2N(CH3)3] H O RCO CH2OPO3H2 CH2OCR O Phosphatidic acid H O RCO CH2OH CH2OCR O Diacylglycerol H O RCO CH2OCR CH2OCR O O Triacylglycerol H2O RCSCoA O X Lecithin is added to foods such as mayonnaise as an emulsifying agent to prevent the fat and water from sepa￾rating into two layers. HO H CH2OPO3H2 CH2OH L-Glycerol 3-phosphate O RCSCoA O RCSCoA Two acyl coenzyme A molecules (R and R may be the same or they may be different) H O RCO CH2OPO3H2 CH2OCR O Phosphatidic acid 2HSCoA Coenzyme A Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website

26.4 Phospholipids o CHOCK H CH,OPO OCH,CH,N(CH3)3 Phosphatidylcholine (R and rare usually Phosphatidylcholine possesses a polar"head group"(the positively charged choline and negatively charged phosphate units) and two nonpolar""tails"(the acyl groups) Under certain conditions, such as at the interface of two aqueous phases, phosphatidyl- choline forms what is called a lipid bilayer, as shown in Figure 26.4. Because there are two long-chain acyl groups in each molecule, the most stable assembly has the polar groups solvated by water molecules at the top and bottom surfaces and the lipophilic acyl groups directed toward the interior of the bilayer. Phosphatidylcholine is one of the principal components of cell membranes. These membranes are composed of lipid bilayers analogous to those of Figure 26. 4. Nonpola materials can diffuse through the bilayer from one side to the other relatively easily; polar materials, particularly metal ions such as Na, K, and Ca*+, cannot. The transport of metal ions through a membrane is usually assisted by certain proteins present in the lipid bilayer, which contain a metal ion binding site surrounded by a lipophilic exterior. The metal ion is picked up at one side of the lipid bilayer and delivered at the other, sur- rounded at all times by a polar environment on its passage through the hydrocarbon-like interior of the membrane lonophore antibiotics such as monensin(Section 16. 4)disrupt the normal functioning of cells by facilitating metal ion transport across cell membranes Hydrophilic 88888 Hydrophilic head groups FIGURE 26.4 Cross section of a phospholipid bilayer. Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

26.4 Phospholipids 1023 Phosphatidylcholine possesses a polar “head group” (the positively charged choline and negatively charged phosphate units) and two nonpolar “tails” (the acyl groups). Under certain conditions, such as at the interface of two aqueous phases, phosphatidyl￾choline forms what is called a lipid bilayer, as shown in Figure 26.4. Because there are two long-chain acyl groups in each molecule, the most stable assembly has the polar groups solvated by water molecules at the top and bottom surfaces and the lipophilic acyl groups directed toward the interior of the bilayer. Phosphatidylcholine is one of the principal components of cell membranes. These membranes are composed of lipid bilayers analogous to those of Figure 26.4. Nonpolar materials can diffuse through the bilayer from one side to the other relatively easily; polar materials, particularly metal ions such as Na, K, and Ca2, cannot. The transport of metal ions through a membrane is usually assisted by certain proteins present in the lipid bilayer, which contain a metal ion binding site surrounded by a lipophilic exterior. The metal ion is picked up at one side of the lipid bilayer and delivered at the other, sur￾rounded at all times by a polar environment on its passage through the hydrocarbon-like interior of the membrane. Ionophore antibiotics such as monensin (Section 16.4) disrupt the normal functioning of cells by facilitating metal ion transport across cell membranes. H O RCO CH2OPO2  CH2OCR O OCH2CH2N(CH3)3 Phosphatidylcholine (R and R are usually different) Water Water Hydrophilic head groups Hydrophilic head groups Lipophilic tails Lipophilic tails FIGURE 26.4 Cross section of a phospholipid bilayer. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website

1024 CHAPTER TWENTY-SIX Lipids 26.5 WAXES Waxes are water-repelling solids that are part of the protective coatings of a number of living things, including the leaves of plants, the fur of animals, and the feathers of birds hey are usually mixtures of esters in which both the alkyl and acyl group are unbranched and contain a dozen or more carbon atoms. Beeswax, for example, contains the ester triacontyl hexadecanoate as one component of a complex mixture of hydrocar- bons. alcohols. and esters CH3(CH2)14COCH,(CH2)28CH3 Triacontyl hexadecanoate PROBLEM 26.5 Spermaceti is a wax obtained from the sperm whale. It contains among other materials, an ester known as cetyl palmitate, which is used as an emollient in a number of soaps and cosmetics. The systematic name for cetyl palmitate is hexadecyl hexadecanoate. Write a structural formula for this sub- Fatty acids normally occur naturally as esters; fats, oils, phospholipids, and waxes all are unique types of fatty acid esters. There is, however, an important class of fatty acid derivatives that exists and carries out its biological role in the form of the free acid This class of fatty acid derivatives is described in the following section 26.6 PROSTAGLANDINS Research in physiology carried out in the 1930s established that the lipid fraction of emen contains small amounts of substances that exert powerful effects on smooth mus- cle. Sheep prostate glands proved to be a convenient source of this material and yielded a mixture of structurally related substances referred to collectively as prostaglandins. We now know that prostaglandins are present in almost all animal tissues, where they carry out a variety of regulatory functions Prostaglandins are extremely potent substances and exert their physiological effects at very small concentrations. Because of this, their isolation was difficult, and it was not until 1960 that the first members of this class, designated PGE and PGFla(Figure 26.5), were obtained as pure compounds. More than a dozen structurally related prostaglandins have since been isolated and identified. All the prostaglandins are 20-carbon carboxylic acids and contain a cyclopentane ring. All have hydroxyl groups at C-ll and C-15(for the numbering of the positions in prostaglandins, see Figure 26.5). Prostaglandins belong ing to the F series have an additional hydroxyl group at C-9, and a carbonyl function is COOH COOH CH FIGURE 26.5 Struc HO tures of two representative Prostaglandin el Prostaglandin Fla bering scheme is illustrated PGEj (PGFla) in the structure of PGE1 Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

1024 CHAPTER TWENTY-SIX Lipids 26.5 WAXES Waxes are water-repelling solids that are part of the protective coatings of a number of living things, including the leaves of plants, the fur of animals, and the feathers of birds. They are usually mixtures of esters in which both the alkyl and acyl group are unbranched and contain a dozen or more carbon atoms. Beeswax, for example, contains the ester triacontyl hexadecanoate as one component of a complex mixture of hydrocar￾bons, alcohols, and esters. PROBLEM 26.5 Spermaceti is a wax obtained from the sperm whale. It contains, among other materials, an ester known as cetyl palmitate, which is used as an emollient in a number of soaps and cosmetics. The systematic name for cetyl palmitate is hexadecyl hexadecanoate. Write a structural formula for this sub￾stance. Fatty acids normally occur naturally as esters; fats, oils, phospholipids, and waxes all are unique types of fatty acid esters. There is, however, an important class of fatty acid derivatives that exists and carries out its biological role in the form of the free acid. This class of fatty acid derivatives is described in the following section. 26.6 PROSTAGLANDINS Research in physiology carried out in the 1930s established that the lipid fraction of semen contains small amounts of substances that exert powerful effects on smooth mus￾cle. Sheep prostate glands proved to be a convenient source of this material and yielded a mixture of structurally related substances referred to collectively as prostaglandins. We now know that prostaglandins are present in almost all animal tissues, where they carry out a variety of regulatory functions. Prostaglandins are extremely potent substances and exert their physiological effects at very small concentrations. Because of this, their isolation was difficult, and it was not until 1960 that the first members of this class, designated PGE1 and PGF1 (Figure 26.5), were obtained as pure compounds. More than a dozen structurally related prostaglandins have since been isolated and identified. All the prostaglandins are 20-carbon carboxylic acids and contain a cyclopentane ring. All have hydroxyl groups at C-11 and C-15 (for the numbering of the positions in prostaglandins, see Figure 26.5). Prostaglandins belong￾ing to the F series have an additional hydroxyl group at C-9, and a carbonyl function is O CH3(CH2)14COCH2(CH2)28CH3 Triacontyl hexadecanoate O HO CH3 COOH Prostaglandin E1 (PGE1) HO HO Prostaglandin F1 (PGF1) HO 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 CH3 COOH HO FIGURE 26.5 Struc￾tures of two representative prosta-glandins. The num￾bering scheme is illustrated in the structure of PGE1. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website