885c07-238-27211/21/037:38 AM Page238Mac113mac11:4EDL chapter CARBOHYDRATES AND GLYCOBIOLOGY 7.1 Monosaccharides and disaccharides 239 attached to proteins or lipids act as signals that deter 7.2 Polysaccharides 247 mine the intracellular location or metabolic fate of these hybrid molecules, called glycoconjugates. This chap 7.3 Glycoconjugates: Proteoglycans, Glycoproteins, ter introduces the major classes of carbohydrates and glycoconjugates and provides a few examples of their 7.4 Carbohydrates as Informational Molecules: many structural and functional roles The Sugar Code 261 Carbohydrates are polyhydroxy aldehydes or ke- 7.5 Working with Carbohydrates 267 tones, or substances that yield such compounds on hy drolysis. Many, but not all, carbohydrates have the em- pirical formula (CHOni some also contain nitrogen, Ah! sweet mystery of life phosphorus, or sulfur. -Rida Johnson Young(lyrics)and Victor Herbert(music), There are three major size classes of carbohydrates Ah! Sweet Mystery of Life, 1910 monosaccharides, oligosaccharides, and polysaccha rides(the word"saccharide"is derived from the greek sakcharom, meaning"sugar). Monosaccharides, or I would feel more optimistic about a bright future for man simple sugars, consist of a single polyhydroxy aldehyde if he spent less time proving that he can outwit Nature or ketone unit. The most abundant monosaccharide in and more time tasting her sweetness and respecting her nature is the six-carbon sugar D-glucose, sometimes re- ferred to as dextrose. Monosaccharides of more than -E.B. White. "Coon Tree. "1977 four carbons tend to have cyclic structures Oligosaccharides consist of short chains of mono- saccharide units, or residues, joined by characteristic carbohydrates are the most abundant biomolecules linkages called glycosidic bonds. The most abundant are on Earth. Each year, photosynthesis converts more the disaccharides, with two monosaccharide units than 100 billion metric tons of COe and HO into cellu- Typical is sucrose(cane sugar), which consists of the lose and other plant products. Certain carbohydrates six-carbon sugars D-glucose and D-fructose. All common (sugar and starch) are a dietary staple in most parts of monosaccharides and disaccharides have names ending the world, and the oxidation of carbohydrates is the cen- with the suffix "-ose "In cells, most oligosaccharides tral energy-yielding pathway in most nonphotosynthetic consisting of three or more units do not occur as free cells. Insoluble carbohydrate polymers serve as struc- entities but are joined to nonsugar molecules (lipids or tural and protective elements in the cell walls of bacte- proteins) in glycoconjugates ria and plants and in the connective tissues of animals. The polysaccharides are sugar polymers contain- Other carbohydrate polymers lubricate skeletal joints ing more than 20 or so monosaccharide units, and some and participate in recognition and adhesion between have hundreds or thousands of units. Some polysac cells. More complex carbohydrate polymers covalently charides, such as cellulose, are linear chains; others
chapter Carbohydrates are the most abundant biomolecules on Earth. Each year, photosynthesis converts more than 100 billion metric tons of CO2 and H2O into cellulose and other plant products. Certain carbohydrates (sugar and starch) are a dietary staple in most parts of the world, and the oxidation of carbohydrates is the central energy-yielding pathway in most nonphotosynthetic cells. Insoluble carbohydrate polymers serve as structural and protective elements in the cell walls of bacteria and plants and in the connective tissues of animals. Other carbohydrate polymers lubricate skeletal joints and participate in recognition and adhesion between cells. More complex carbohydrate polymers covalently attached to proteins or lipids act as signals that determine the intracellular location or metabolic fate of these hybrid molecules, called glycoconjugates. This chapter introduces the major classes of carbohydrates and glycoconjugates and provides a few examples of their many structural and functional roles. Carbohydrates are polyhydroxy aldehydes or ketones, or substances that yield such compounds on hydrolysis. Many, but not all, carbohydrates have the empirical formula (CH2O)n; some also contain nitrogen, phosphorus, or sulfur. There are three major size classes of carbohydrates: monosaccharides, oligosaccharides, and polysaccharides (the word “saccharide” is derived from the Greek sakcharon, meaning “sugar”). Monosaccharides, or simple sugars, consist of a single polyhydroxy aldehyde or ketone unit. The most abundant monosaccharide in nature is the six-carbon sugar D-glucose, sometimes referred to as dextrose. Monosaccharides of more than four carbons tend to have cyclic structures. Oligosaccharides consist of short chains of monosaccharide units, or residues, joined by characteristic linkages called glycosidic bonds. The most abundant are the disaccharides, with two monosaccharide units. Typical is sucrose (cane sugar), which consists of the six-carbon sugars D-glucose and D-fructose. All common monosaccharides and disaccharides have names ending with the suffix “-ose.” In cells, most oligosaccharides consisting of three or more units do not occur as free entities but are joined to nonsugar molecules (lipids or proteins) in glycoconjugates. The polysaccharides are sugar polymers containing more than 20 or so monosaccharide units, and some have hundreds or thousands of units. Some polysaccharides, such as cellulose, are linear chains; others, CARBOHYDRATES AND GLYCOBIOLOGY 7.1 Monosaccharides and Disaccharides 239 7.2 Polysaccharides 247 7.3 Glycoconjugates: Proteoglycans, Glycoproteins, and Glycolipids 255 7.4 Carbohydrates as Informational Molecules: The Sugar Code 261 7.5 Working with Carbohydrates 267 Ah! sweet mystery of life . . . —Rida Johnson Young (lyrics) and Victor Herbert (music), “Ah! Sweet Mystery of Life,” 1910 I would feel more optimistic about a bright future for man if he spent less time proving that he can outwit Nature and more time tasting her sweetness and respecting her seniority. —E. B. White, “Coon Tree,” 1977 7 238 8885d_c07_238-272 11/21/03 7:38 AM Page 238 Mac113 mac113:122_EDL:
885d_c07-238-27211/21/037:38 AM Page239Mac113mac113:1aEDL Chapter 7 Carbohydrates and Glycobiology such as glycogen, are branched. Both glycogen and cel lulose consist of recurring units of D-glucose, but they differ in the type of glycosidic linkage and consequently have strikingly different properties and biological roles -C-OH H-C-OH H-C-OH 7. 1 Monosaccharides and disaccharides Glyceraldehyde, Dihydroxyacetone The simplest of the carbohydrates, the monosaccha rides, are either aldehydes or ketones with two or more ydroxyl groups; the six-carbon monosaccharides glu cose and fructose have five hydroxyl groups. Many of the carbon atoms to which hydroxyl groups are attached -C-OH are chiral centers, which give rise to the many sugar H-C-OH stereoisomers found in nature. We begin by describing HO-C-H HO-C-H the families of monosaccharides with backbones of three to seven carbons-their structure and stereoisomeric H-C-OH H-C-OH forms, and the means of representing their three- H-C-OH H-C-OH imensional structures on paper. We then discuss sev CH,OH CHOH eral chemical reactions of the carbonyl groups of mono- saccharides. One such reaction the addition of a hydroxyl group from within the same molecule, gener- ates the cyclic forms of five- and six-carbon sugars(the forms that predominate in aqueous solution) and cre- H ates a new chiral center, adding further stereochemical complexity to this class of compounds. The nomencla- HC-OH ture for unambiguously specifying the configuration about each carbon atom in a cyclic form and the means H-C-OH H-C-OH of representing these structures on paper are therefore H-C-OH H-C- described in some detail: this information willl be useful as we discuss the metabolism of monosaccharides in CHOOH CHOH Part Il. We also introduce here some important mono- an aldopentose saccharide derivatives encountered in later chapters. The Two Families of monosaccharides are aldoses FIGURE 7-1 Representative monosaccharides. (a) Two trioses, an and Ketoses aldose and a ketose. The carbonyl group in each is shaded. (b)Two common hexoses. (c) The pentose components of nucleic acids Monosaccharides are colorless, crystalline solids that D-Ribose is a component of ribonucleic acid(RNA), and 2-deoxy-D- are freely soluble in water but insoluble in nonpolar sol ribose is a component of deoxyribonucleic acid (DNA) vents. Most have a sweet taste. The backbones of com- mon monosaccharide molecules are unbranched carbon chains in which all the carbon atoms are linked by sin- aldotetroses and ketotetroses, aldopentoses and ke- gle bonds. In the open-chain form, one of the carbon topentoses, and so on. The hexoses, which include the atoms is double-bonded to an oxygen atom to form a aldohexose D-glucose and the ketohexose D-fructose carbonyl group; each of the other carbon atoms has a (Fig. 7-1b), are the most common monosaccharides in hydroxyl group. If the carbonyl group is at an end of the ture. The aldopentoses D-ribose and 2-deoxy-D-ribose carbon chain(that is, in an aldehyde group) the mono- (Fig. 7-lc)are components of nucleotides and nucleic saccharide is an aldose; if the carbonyl group is at any acids(Chapter 8) other position (in a ketone group) the monosaccharide is a ketose. The simplest monosaccharides are the two Monosaccharides Have Asymmetric Centers three-carbon trioses: glyceraldehyde, an aldotriose, and All the monosaccharides except dihydroxyacetone con dihydroxyacetone, a ketotriose(Fig. 7-la) tain one or more asymmetric(chiral) carbon atoms and Monosaccharides with four, five, six, and seven car- thus occur in optically active isomeric forms(pp. 17- bon atoms in their backbones are called, respectively, 19). The simplest aldose, glyceraldehyde, contains one tetroses, pentoses, hexoses, and heptoses. There are chiral center (the middle carbon atom) and therefore has aldoses and ketoses of each of these chain lengths: two different optical isomers, or enantiomers(Fig. 7-2)
Chapter 7 Carbohydrates and Glycobiology 239 such as glycogen, are branched. Both glycogen and cellulose consist of recurring units of D-glucose, but they differ in the type of glycosidic linkage and consequently have strikingly different properties and biological roles. 7.1 Monosaccharides and Disaccharides The simplest of the carbohydrates, the monosaccharides, are either aldehydes or ketones with two or more hydroxyl groups; the six-carbon monosaccharides glucose and fructose have five hydroxyl groups. Many of the carbon atoms to which hydroxyl groups are attached are chiral centers, which give rise to the many sugar stereoisomers found in nature. We begin by describing the families of monosaccharides with backbones of three to seven carbons—their structure and stereoisomeric forms, and the means of representing their threedimensional structures on paper. We then discuss several chemical reactions of the carbonyl groups of monosaccharides. One such reaction, the addition of a hydroxyl group from within the same molecule, generates the cyclic forms of five- and six-carbon sugars (the forms that predominate in aqueous solution) and creates a new chiral center, adding further stereochemical complexity to this class of compounds. The nomenclature for unambiguously specifying the configuration about each carbon atom in a cyclic form and the means of representing these structures on paper are therefore described in some detail; this information will be useful as we discuss the metabolism of monosaccharides in Part II. We also introduce here some important monosaccharide derivatives encountered in later chapters. The Two Families of Monosaccharides Are Aldoses and Ketoses Monosaccharides are colorless, crystalline solids that are freely soluble in water but insoluble in nonpolar solvents. Most have a sweet taste. The backbones of common monosaccharide molecules are unbranched carbon chains in which all the carbon atoms are linked by single bonds. In the open-chain form, one of the carbon atoms is double-bonded to an oxygen atom to form a carbonyl group; each of the other carbon atoms has a hydroxyl group. If the carbonyl group is at an end of the carbon chain (that is, in an aldehyde group) the monosaccharide is an aldose; if the carbonyl group is at any other position (in a ketone group) the monosaccharide is a ketose. The simplest monosaccharides are the two three-carbon trioses: glyceraldehyde, an aldotriose, and dihydroxyacetone, a ketotriose (Fig. 7–1a). Monosaccharides with four, five, six, and seven carbon atoms in their backbones are called, respectively, tetroses, pentoses, hexoses, and heptoses. There are aldoses and ketoses of each of these chain lengths: aldotetroses and ketotetroses, aldopentoses and ketopentoses, and so on. The hexoses, which include the aldohexose D-glucose and the ketohexose D-fructose (Fig. 7–1b), are the most common monosaccharides in nature. The aldopentoses D-ribose and 2-deoxy-D-ribose (Fig. 7–1c) are components of nucleotides and nucleic acids (Chapter 8). Monosaccharides Have Asymmetric Centers All the monosaccharides except dihydroxyacetone contain one or more asymmetric (chiral) carbon atoms and thus occur in optically active isomeric forms (pp. 17– 19). The simplest aldose, glyceraldehyde, contains one chiral center (the middle carbon atom) and therefore has two different optical isomers, or enantiomers (Fig. 7–2). H C O OH Dihydroxyacetone, a ketotriose A C OH C H H H H C OH A H C OH H Glyceraldehyde, an aldotriose O C H (a) (b) D-Fructose, a ketohexose C O OH C C H C H H HO CH2OH H OH H C OH D-Glucose, an aldohexose C OH C C H H HO CH2OH H OH H C OH O C H (c) 2-Deoxy-D-ribose, an aldopentose C OH O C H H CH2 H C OH D-Ribose, an aldopentose C OH H C H CH2OH OH H C OH CH2OH O C H FIGURE 7–1 Representative monosaccharides. (a) Two trioses, an aldose and a ketose. The carbonyl group in each is shaded. (b) Two common hexoses. (c) The pentose components of nucleic acids. D-Ribose is a component of ribonucleic acid (RNA), and 2-deoxy-Dribose is a component of deoxyribonucleic acid (DNA). 8885d_c07_238-272 11/21/03 7:38 AM Page 239 Mac113 mac113:122_EDL:
885d_c07-238-27211/21/037:38 AM Page240Mac113mac113:1aEDL 240 Part I Structure and Catalysis of each carbon-chain length can be divided into two groups that differ in the configuration about the chiral center most distant from the carbonyl carbon. Those in which the configuration at this reference carbon is the same as that of D-glyceraldehyde are designated D CHO CHO isomers, and those with the same configuration as L- glyceraldehyde are L isomers. When the hydroxyl group on the reference carbon is on the right in the projection formula, the sugar is the D isomer; when on the left, it is the L isomer Of the 16 possible aldohexoses, eight are D forms and eight are L. Most of the hexoses of living organisms are D isomers CH2OH Figure 7-3 shows the structures of the D stereoiso- mers of all the aldoses and ketoses having three to six carbon atoms. The carbons of a sugar are numbered be- ginning at the end of the chain nearest the carbonyl Ball-and-stick models group. Each of the eight D-aldohexoses, which differ in the stereochemistry at C-2, C-3, or C-4, has its own name: D-glucose, D-galactose, D-mannose, and so forth CHO CHO (Fig. 7-3a). The four- and five-carbon ketoses are des H-C-OH HO--C-H ignated by inserting"ul"into the name of a correspond ing aldose; for example, D-ribulose is the ketopentose CH,OH CH,OH corresponding to the aldopentose D-ribose. The keto- hexoses are named otherwise: for example, fructose (from the Latin fructus, fruit"; fruits are rich in this Fischer projection formulas sugar) and sorbose (from Sorbus, the genus of moun- tain ash, which has berries rich in the related sugar al- cohol sorbitol). Two sugars that differ only in the con figuration around one carbon atom are called epimers; H-C-OH HO-C-H D-glucose and D-mannose, which differ only in the stere- ochemistry at C-2, are epimers, as are D-glucose and D- CHOH CH。OH galactose(which differ at C-4)(Fig. 7-4) L-Glyceraldehyde Some sugars occur naturally in their L form; exam ples are L-arabinose and the L isomers of some sugar de- rivatives that are common components of glycoconju- FIGURE 7-2 Three ways to represent the two stereoisomers of glyc- gates(Section 7.3) eraldehyde. The stereoisomers are mirror images of each other. Ball- H O and-stick models show the actual configuration of molecules By con- vention, in Fischer projection formulas, horizontal bonds project out H-C-OHl of the plane of the paper, toward the reader; vertical bonds project ehind the plane of the paper, away from the reader. Recall (see Fig HO-C-H 1-17)that in perspective formulas, solid wedge-shaped bonds point toward the reader, dashed wedges point away CHOH By convention, one of these two forms is designated the The Common Monosaccharides D isomer the other the l isomer. as for other biomole cules with chiral centers, the absolute configurations of Have Cyclic Structures sugars are known from x-ray crystallography. To repre- For simplicity, we have thus far represented the struc sent three-dimensional sugar structures on paper, we tures of aldoses and ketoses as straight-chain molecules often use Fischer projection formulas (Fig. 7-2) (Figs 7-3, 7-4). In fact, in aqueous solution, aldotet- In general, a molecule with n chiral centers can roses and all monosaccharides with five or more carbon have 2" stereoisomers. Glyceraldehyde has 2=2; the atoms in the backbone occur predominantly as cyclic aldohexoses, with four chiral centers, have 2=16 (ring) structures in which the carbonyl group has stereoisomers. The stereoisomers of monosaccharides formed a covalent bond with the oxygen of a hydroxyl
By convention, one of these two forms is designated the D isomer, the other the L isomer. As for other biomolecules with chiral centers, the absolute configurations of sugars are known from x-ray crystallography. To represent three-dimensional sugar structures on paper, we often use Fischer projection formulas (Fig. 7–2). In general, a molecule with n chiral centers can have 2n stereoisomers. Glyceraldehyde has 21 2; the aldohexoses, with four chiral centers, have 24 16 stereoisomers. The stereoisomers of monosaccharides of each carbon-chain length can be divided into two groups that differ in the configuration about the chiral center most distant from the carbonyl carbon. Those in which the configuration at this reference carbon is the same as that of D-glyceraldehyde are designated D isomers, and those with the same configuration as Lglyceraldehyde are L isomers. When the hydroxyl group on the reference carbon is on the right in the projection formula, the sugar is the D isomer; when on the left, it is the L isomer. Of the 16 possible aldohexoses, eight are D forms and eight are L. Most of the hexoses of living organisms are D isomers. Figure 7–3 shows the structures of the D stereoisomers of all the aldoses and ketoses having three to six carbon atoms. The carbons of a sugar are numbered beginning at the end of the chain nearest the carbonyl group. Each of the eight D-aldohexoses, which differ in the stereochemistry at C-2, C-3, or C-4, has its own name: D-glucose, D-galactose, D-mannose, and so forth (Fig. 7–3a). The four- and five-carbon ketoses are designated by inserting “ul” into the name of a corresponding aldose; for example, D-ribulose is the ketopentose corresponding to the aldopentose D-ribose. The ketohexoses are named otherwise: for example, fructose (from the Latin fructus, “fruit”; fruits are rich in this sugar) and sorbose (from Sorbus, the genus of mountain ash, which has berries rich in the related sugar alcohol sorbitol). Two sugars that differ only in the configuration around one carbon atom are called epimers; D-glucose and D-mannose, which differ only in the stereochemistry at C-2, are epimers, as are D-glucose and Dgalactose (which differ at C-4) (Fig. 7–4). Some sugars occur naturally in their L form; examples are L-arabinose and the L isomers of some sugar derivatives that are common components of glycoconjugates (Section 7.3). The Common Monosaccharides Have Cyclic Structures For simplicity, we have thus far represented the structures of aldoses and ketoses as straight-chain molecules (Figs 7–3, 7–4). In fact, in aqueous solution, aldotetroses and all monosaccharides with five or more carbon atoms in the backbone occur predominantly as cyclic (ring) structures in which the carbonyl group has formed a covalent bond with the oxygen of a hydroxyl L-Arabinose C O A A A A O O O C OH H OCO H HO H CH2OH HO O C H G J 240 Part I Structure and Catalysis FIGURE 7–2 Three ways to represent the two stereoisomers of glyceraldehyde. The stereoisomers are mirror images of each other. Balland-stick models show the actual configuration of molecules. By convention, in Fischer projection formulas, horizontal bonds project out of the plane of the paper, toward the reader; vertical bonds project behind the plane of the paper, away from the reader. Recall (see Fig. 1–17) that in perspective formulas, solid wedge-shaped bonds point toward the reader, dashed wedges point away. Mirror CH2OH Ball-and-stick models CH2OH CHO CHO OH H H OH CHO C H CH2OH HO L-Glyceraldehyde Perspective formulas L-Glyceraldehyde C CH2OH H CHO CHO CHO H C OH CH2OH D-Glyceraldehyde OH D-Glyceraldehyde C CH2OH H HO Fischer projection formulas 8885d_c07_238-272 11/21/03 7:38 AM Page 240 Mac113 mac113:122_EDL:
885d_c07-238-27211/21/037:38 AM Page241Mac113mac113:1aEDL Chapter 7 Carbohydrates and Glycobiology 241 Four carbons Five carbons H O H 0 H O H O H-C-oH HO- H-C-oH HO-C-H H-C-oH H--C-OH HO H-C-OH H-C-OH H→C-OH H-C-OH H OH HoH OH D-Glyceraldehyde D-ErythroseD-Threose D-Ribose [D-Arabinose Xylo L Six carbons H O H O H 0 H O H O H H O H O H-C-OH o-C-H OHHo→-H HC- OH HO-C—H H-C-OH HO-C-H H--C-O H-C-oH HO-C-H HO→C-H H-C-oHH-C-oh HO-C-H HO-C-H H-C-ohH-C-oh H-C-oh H-C-oh HO--C-H Ho--C-h Ho--c-h Ho-C-H OH H-C-oH H-C-oH H-C-oH H-C-oH H-C-oH D-Glucose D-Mannose D-Gulose D-Idose D-Galactose DAldoses Three carbons our carbons FIGURE 7-3 Aldoses and ketoses. The series of (a)D-aldoses and (b)Ketoses having from three to six carbon atoms, shown as CH2OH projection formulas. The carbon atoms in red are chiral centers. In all these D isomers, the chiral carbon most distant from the carbonyl carbon has the same configuration as the chiral carbon OH in D-glyceraldehyde. The sugars named in boxes are the most Dihydroxyacetone common in nature; you will encounter these again in this and Five carbons Six carbons CHOH CHoO CHOO C=0 H-C-OH O-C-H H-C-OH H-C-OH H-C-OH -C-OH D-Ribulose cho CHO H-C-OH H-C-OHI CHoO CHoO HO-°C-H CH,OH C-O H-C-OH HOC—H C=O HO-C-H H-C-OH HOH D-Glucose D-Galactose CH2OH CH2OH at C-2) (epimer at C-4) D-Xylulose D-Sorbose FIGURE 7-4 Epimers. D-Glucose and two of its epimers are shown D-Ketoses as projection formulas. Each epimer differs from D-glucose in the con figuration at one chiral center(shaded red)
Chapter 7 Carbohydrates and Glycobiology 241 D-Aldoses (a) Six carbons Three carbons H O C H C OH CH2OH D-Ribose H C OH H OH C H C O OH CH2OH D-Glyceraldehyde H C C H O CH2OH D-Threose C H C OH HO H H C O OH CH2OH D-Erythrose H C H C OH H C O OH CH2OH D-Allose C H C OH H OH C H C OH H HO C H CH2OH D-Lyxose H C OH C H HO H O C H C OH CH2OH D-Xylose H C OH HO C H H O C C H CH2OH D-Arabinose H C OH H OH C HO H O C C H CH2OH D-Talose H C OH C H C H HO HO HO H O C H C OH CH2OH D-Gulose H C OH C H H C OH HO H O C HO C H CH2OH D-Mannose H C H C OH C H OH HO H O C H C OH CH2OH D-Glucose H C OH H OH C HO C H H O C Four carbons C H CH2OH D-Idose H C OH C H H C OH HO HO H O C H C OH CH2OH D-Galactose H C OH C H HO C H HO H O C C H CH2OH D-Altrose H C OH H OH C H C OH HO O C H Five carbons D-Ketoses (b) H OH O D-Ribulose CH2OH C CH2OH C H C OH H OH O D-Psicose CH2OH C CH2OH C H C OH H C OH HO H O D-Fructose CH2OH C CH2OH C H C OH H C OH H O D-Tagatose CH2OH C CH2OH C H C OH C H HO HO O D-Sorbose CH2OH C CH2OH C OH H C C H HO OH H Dihydroxyacetone CH2OH C CH2OH O Three carbons Five carbons Six carbons Four carbons O D-Xylulose CH2OH C CH2OH C OH H H C HO H OH O D-Erythrulose CH2OH C CH2OH C FIGURE 7–3 Aldoses and ketoses. The series of (a) D-aldoses and (b) D-ketoses having from three to six carbon atoms, shown as projection formulas. The carbon atoms in red are chiral centers. In all these D isomers, the chiral carbon most distant from the carbonyl carbon has the same configuration as the chiral carbon in D-glyceraldehyde. The sugars named in boxes are the most common in nature; you will encounter these again in this and later chapters. H C OH CH2OH D-Mannose (epimer at C-2) C HO C H C CHO 6 1 2 3 4 5 H C OH CH2OH D-Glucose H C HO C H OH H C OH CHO 6 1 2 3 4 5 H C OH CH2OH D-Galactose (epimer at C-4) H C HO C H OH C CHO 6 1 2 3 4 5 H OH HO H HO H FIGURE 7–4 Epimers. D-Glucose and two of its epimers are shown as projection formulas. Each epimer differs from D-glucose in the configuration at one chiral center (shaded red). 8885d_c07_238-272 11/21/03 7:38 AM Page 241 Mac113 mac113:122_EDL:
88607238-2721/21/037:38 AM Page242ac113ac11:aEDL 242 Part I Structure and Catalysis OH HO- o-R =R- R- -C-oR+H,o H Ho—R Aldehyde Alcohol Hemiacetal Acetal FIGURE 7-5 Formation of hemiacetals and hemiketals An aldehyde or ketone can react with an alcohol in a 1:1 ratio to yield a hemiacetal or hemiketal, respectively, creating a new chiral center at the carbonyl carbon. r- -C=0+HO- eRCOR+Ho Substitution of a second alcohol molecule produces HO-R nother sugar molecule, the bond produced is a glycosidic bond (p 245 group along the chain. The formation of these ring struc- istry of ring forms of monosaccharides. However, the tures is the result of a general reaction between alco- six-membered pyranose ring is not planar, as Haworth hols and aldehydes or ketones to form derivatives called perspectives suggest, but tends to assume either of two hemiacetals or hemiketals (Fig. 7-5), which contain"chair" conformations(Fig. 7-8). Recall from Chapter 1 an additional asymmetric carbon atom and thus can ex (p. 19) that two conformations of a molecule are in- ist in two stereoisomeric forms. For example, D-glucose terconvertible without the breakage of covalent bonds exists in solution as an intramolecular hemiacetal in which the free hydroxyl group at C-5 has reacted with the aldehydic C-l, rendering the latter carbon asyn metric and producing two stereoisomers, designated a and B(Fig. 7-6). These six-membered ring compounds are called pyranoses because they resemble the six- membered ring compound pyran(Fig. 7-0. The sys- tematic names for the two ring forms of D-glucose ar a-D-glucopyranose and B-D-glucopyranose H-C-OH Aldohexoses also exist in cyclic forms having five- membered rings, which, because they resemble the five- CH2OH membered ring compound furan, are called furanoses However, the six-membered aldopyranose ring is much more stable than the aldofuranose ring and predomi- CH2OH ates in aldohexose solutions. Only aldoses having five -OH or more carbon atoms can form pyranose rings Isomeric forms of monosaccharides that differ only in their configuration about the hemiacetal or heike- tal carbon atom are called anomers. The hemiacetal (or carbonyl) carbon atom is called the anomeric carbon. The a and B anomers of D-glucose interconvert in aque ous solution by a process called mutarotation. Thus a solution of a-D-glucose and a solution of B-D-glucose eventually form identical equilibrium mixtures having 6CH2OH 6CH2OH identical optical properties. This mixture consists of about one-third a-D-glucose, two-thirds B-D-glucose and very small amounts of the linear and five-membered ring(glucofuranose) forms OH H Ketohexoses also occur in a and B anomeric forms In these compounds the hydroxyl group at C-5(or C-6) reacts with the keto group at C-2, forming a furanose Cor pyranose)ring containing a hemiketal linkage (Fig. FIGURE 7-6 Formation of the two cyclic forms of D-glucose. Read 7-5). D-Fructose readily forms the furanose ring (Fig. tion between the aldehyde group at C-1 and the hydroxyl group at 7-7); the more common anomer of this sugar in com- C-5 forms a hemiacetal linkage, producing either of two stereoiso- bined forms or in derivatives is B-D-fructofuranose mers, the a and B anomers, which differ only in the stereochemistry Haworth perspective formulas like those in Fig- around the hemiacetal carbon. The interconversion of a and B anomers ure 7-7 are commonly used to show the stereochem- is called mutarotation
242 Part I Structure and Catalysis H C -D-Glucopyranose C H OH H 1 5 C 6CH2OH 4 C OH CH2OH 6 C 5 HO H OH C H 3 H C 4 HO C3 OH H H 2 OH C 1 5 6CH2OH 4 C O OH HO OH C H H C3 H C H H 2 OH OH C 1 5 6CH2OH 4 C O HO OH C H H C3 H C H H 2 OH OH D-Glucose -D-Glucopyranose H C O O 1C H 2 FIGURE 7–6 Formation of the two cyclic forms of D-glucose. Reaction between the aldehyde group at C-1 and the hydroxyl group at C-5 forms a hemiacetal linkage, producing either of two stereoisomers, the and anomers, which differ only in the stereochemistry around the hemiacetal carbon. The interconversion of and anomers is called mutarotation. FIGURE 7–5 Formation of hemiacetals and hemiketals. An aldehyde or ketone can react with an alcohol in a 1:1 ratio to yield a hemiacetal or hemiketal, respectively, creating a new chiral center at the carbonyl carbon. Substitution of a second alcohol molecule produces an acetal or ketal. When the second alcohol is part of another sugar molecule, the bond produced is a glycosidic bond (p. 245). istry of ring forms of monosaccharides. However, the six-membered pyranose ring is not planar, as Haworth perspectives suggest, but tends to assume either of two “chair” conformations (Fig. 7–8). Recall from Chapter 1 (p. 19) that two conformations of a molecule are interconvertible without the breakage of covalent bonds, R3 O HO C Ketal R1 C OR4 R 1 H Aldehyde Hemiketal R2 HO C H OH R 1 OR3 Hemiacetal OR3 R2 R 1 C O R2 Alcohol H2O C H2O OH R1 OR2 Ketone Alcohol C H Acetal OR3 OR2 HO R4 R2 R1 HO R4 HO R3 HO R3 group along the chain. The formation of these ring structures is the result of a general reaction between alcohols and aldehydes or ketones to form derivatives called hemiacetals or hemiketals (Fig. 7–5), which contain an additional asymmetric carbon atom and thus can exist in two stereoisomeric forms. For example, D-glucose exists in solution as an intramolecular hemiacetal in which the free hydroxyl group at C-5 has reacted with the aldehydic C-1, rendering the latter carbon asymmetric and producing two stereoisomers, designated and (Fig. 7–6). These six-membered ring compounds are called pyranoses because they resemble the sixmembered ring compound pyran (Fig. 7–7). The systematic names for the two ring forms of D-glucose are -D-glucopyranose and -D-glucopyranose. Aldohexoses also exist in cyclic forms having fivemembered rings, which, because they resemble the fivemembered ring compound furan, are called furanoses. However, the six-membered aldopyranose ring is much more stable than the aldofuranose ring and predominates in aldohexose solutions. Only aldoses having five or more carbon atoms can form pyranose rings. Isomeric forms of monosaccharides that differ only in their configuration about the hemiacetal or hemiketal carbon atom are called anomers. The hemiacetal (or carbonyl) carbon atom is called the anomeric carbon. The and anomers of D-glucose interconvert in aqueous solution by a process called mutarotation. Thus, a solution of -D-glucose and a solution of -D-glucose eventually form identical equilibrium mixtures having identical optical properties. This mixture consists of about one-third -D-glucose, two-thirds -D-glucose, and very small amounts of the linear and five-membered ring (glucofuranose) forms. Ketohexoses also occur in and anomeric forms. In these compounds the hydroxyl group at C-5 (or C-6) reacts with the keto group at C-2, forming a furanose (or pyranose) ring containing a hemiketal linkage (Fig. 7–5). D-Fructose readily forms the furanose ring (Fig. 7–7); the more common anomer of this sugar in combined forms or in derivatives is -D-fructofuranose. Haworth perspective formulas like those in Figure 7–7 are commonly used to show the stereochem- 8885d_c07_238-272 11/21/03 7:38 AM Page 242 Mac113 mac113:122_EDL:
88507-238-27211/21/037:38 AM Page243ac113mac11:4EDL Chapter 7 Carbohydrates and Glycobiology CHOH the hydroxyl group at C-6 of L-galactose or L-mannose produces L-fucose or L-rhamnose, respectively; these HOCH2O、1CH2OH deoxy sugars are found in plant polysaccharides and in OH H H HO the complex oligosaccharide components of glycopro- Oxidation of the carbonyl (aldehyde) carbon of glu- a-D-Fructofuranose cose to the carboxyl level produces gluconic acid; other aldoses yield other aldonic acids. Oxidation of the car- bon at the other end of the carbon chain--C-6 of glucose galactose, or mannose--forms the corresponding uronic acid: glucuronic, galacturonic, or mannuronic acid. Both HO\OH H aldonic and uronic acids form stable intramolecular es- CH2OH ters called lactones(Fig. 7-9, lower left). In addition to H OH OH H these acidic hexose derivatives. one nine-carbon acidic B-D-Glucopyranose B-D-Fructofuranose ugar deserves mention: N-acetylneuraminic acid (a sialic acid, but often referred to simply as"sialic acid), a de- HC-0 rivative of N-acetylmannosamine, is a component of many glycoproteins and glycolipids in animals. The carboxylic CH acid groups of the acidic sugar derivatives are ionized at pH 7, and the compounds are therefore correctly named as the carboxylates-glucuronate, galacturonate, and so forth FIGURE 7-7 Pyranoses and furanoses. The pyranose forms of D- glucose and the furanose forms of D-fructose are shown here as Haworth perspective formulas. The edges of the ring nearest the reader are represented by bold lines. Hydroxyl groups below the plane of the ring in these Haworth perspectives would appear at the right side of a Fischer projection(compare with Fig. 7-6). Pyran and furan are whereas two configurations can be interconverted only Two possible chair forms by breaking a covalent bond--for example, in the case of c and B configurations, the bond involving the ring oxygen atom. The specific three-dimensional confor mations of the monosaccharide units are important in determining the biological properties and functions of some polysaccharides, as we shall see Organisms Contain a Variety of Hexose Derivatives H In addition to simple hexoses such as glucose, galactose, nd mannose, there are a number of sugar derivatives in which a hydroxyl group in the parent compound is FIGURE 7-8 Conformational formulas of pyranoses. (a)Two chair replaced with another substituent, or a carbon atom is forms of the pyranose ring Substituents on the ring carbons may be oxidized to a carboxyl group(Fig. 7-9).In glucosamine, either axial (ax), projecting parallel to the vertical axis through the galactosamine, and mannosamine, the hydroxyl at c f the parent compound is replaced with an amino ing, or equatorial (eq), projecting roughly perpendicular to this axis. Two conformers such are these are not readily interconvertible with- group. The amino group is nearly always condensed with out breaking the ring. However, when the molecule is"stretched"( acetic acid, as inN-acetylglucosamine. This glucosamine atomic force microscopy), an input of about 46 k) of energy per mole derivative is part of many structural polymers, includ- of sugar can force the interconversion of chair forms.Generally, sub- ng those of the bacterial cell wall. Bacterial cell walls stituents in the equatorial positions are less sterically hindered by Iso contain a derivative of glucosamine, N-acetylmu neighboring substituents, and conformers with bulky substituents in ramic acid, in which lactic acid (a three-carbon car equatorial positions are favored. Another conformation, the"boat"(not boxylic acid) is ether-linked to the oxygen at C-3 of shown), is seen only in derivatives with very bulky substituents.(b)A N-acetylglucosamine. The substitution of a hydrogen for chair conformation of a-D-glucopyranose
Chapter 7 Carbohydrates and Glycobiology 243 5 2 3 1 4 6 HOCH2 HO O CH2OH OH H -D-Fructofuranose H OH H HOCH2 HO O CH2OH OH H -D-Fructofuranose H OH H -D-Glucopyranose H OH H H H CH2OH O OH H HO OH -D-Glucopyranose 1 3 2 4 H OH H H H O OH H HO OH 5 6CH2OH H2C CH HC O CH Pyran HC HC O CH C H Furan C H FIGURE 7–7 Pyranoses and furanoses. The pyranose forms of Dglucose and the furanose forms of D-fructose are shown here as Haworth perspective formulas. The edges of the ring nearest the reader are represented by bold lines. Hydroxyl groups below the plane of the ring in these Haworth perspectives would appear at the right side of a Fischer projection (compare with Fig. 7–6). Pyran and furan are shown for comparison. ax ax ax eq O O eq eq eq eq eq eq eq eq ax ax ax ax ax ax ax Axis Axis Two possible chair forms (a) eq H H2COH HO OH H HO H H H OH (b) O Axis -D-Glucopyranose FIGURE 7–8 Conformational formulas of pyranoses. (a) Two chair forms of the pyranose ring. Substituents on the ring carbons may be either axial (ax), projecting parallel to the vertical axis through the ring, or equatorial (eq), projecting roughly perpendicular to this axis. Two conformers such are these are not readily interconvertible without breaking the ring. However, when the molecule is “stretched” (by atomic force microscopy), an input of about 46 kJ of energy per mole of sugar can force the interconversion of chair forms. Generally, substituents in the equatorial positions are less sterically hindered by neighboring substituents, and conformers with bulky substituents in equatorial positions are favored. Another conformation, the “boat” (not shown), is seen only in derivatives with very bulky substituents. (b) A chair conformation of -D-glucopyranose. whereas two configurations can be interconverted only by breaking a covalent bond—for example, in the case of and configurations, the bond involving the ring oxygen atom. The specific three-dimensional conformations of the monosaccharide units are important in determining the biological properties and functions of some polysaccharides, as we shall see. Organisms Contain a Variety of Hexose Derivatives In addition to simple hexoses such as glucose, galactose, and mannose, there are a number of sugar derivatives in which a hydroxyl group in the parent compound is replaced with another substituent, or a carbon atom is oxidized to a carboxyl group (Fig. 7–9). In glucosamine, galactosamine, and mannosamine, the hydroxyl at C-2 of the parent compound is replaced with an amino group. The amino group is nearly always condensed with acetic acid, as in N-acetylglucosamine. This glucosamine derivative is part of many structural polymers, including those of the bacterial cell wall. Bacterial cell walls also contain a derivative of glucosamine, N-acetylmuramic acid, in which lactic acid (a three-carbon carboxylic acid) is ether-linked to the oxygen at C-3 of N-acetylglucosamine. The substitution of a hydrogen for the hydroxyl group at C-6 of L-galactose or L-mannose produces L-fucose or L-rhamnose, respectively; these deoxy sugars are found in plant polysaccharides and in the complex oligosaccharide components of glycoproteins and glycolipids. Oxidation of the carbonyl (aldehyde) carbon of glucose to the carboxyl level produces gluconic acid; other aldoses yield other aldonic acids. Oxidation of the carbon at the other end of the carbon chain—C-6 of glucose, galactose, or mannose—forms the corresponding uronic acid: glucuronic, galacturonic, or mannuronic acid. Both aldonic and uronic acids form stable intramolecular esters called lactones (Fig. 7–9, lower left). In addition to these acidic hexose derivatives, one nine-carbon acidic sugar deserves mention: N-acetylneuraminic acid (a sialic acid, but often referred to simply as “sialic acid”), a derivative of N-acetylmannosamine, is a component of many glycoproteins and glycolipids in animals. The carboxylic acid groups of the acidic sugar derivatives are ionized at pH 7, and the compounds are therefore correctly named as the carboxylates—glucuronate, galacturonate, and so forth. 8885d_c07_238-272 11/21/03 7:38 AM Page 243 Mac113 mac113:122_EDL:
88607238-2721/21/037:38 AM Page244ac113ac11:aEDL 244 Part I Structure and Catalysis Glucose family Amino sugars CHoO CH。OH CHOOH CHOH CHoOHI OH H H NH2 H NH HH B-D-Galactosamine B-D-Mannosamine B-D-Glucosamine N-Acetyl-B-D-glucosamine Deoxy sugars CH2-0--POa CHOH CHOO OH H Hg XOH R=-0-C-H H HH HO 00 H NHo OH OH C=0 B-pD-Glucose 6-phosphate Muramic acid N-Acetylmuramie acid B-L-Fi g-L-Rhamnose CH3 CHoO H-C-OH CHoO B-D-Glucuronate D-Gluconate D-Glucono-s-lactone N-Acetylneuraminic acid (a sialic acid) FIGURE 7-9 Some hexose derivatives important in biology. In amino mers. The acidic sugars contain a carboxylate group, which confers a sugars,an-NH2 group replaces one of the -OH groups in the par- negative charge at neutral pH. D-Glucono-8-lactone results from for- ent hexose. Substitution of -H for -OH produces a deoxy sugar; mation of an ester linkage between the C-1 carboxylate group and the note that the deoxy sugars shown here occur in nature as the L iso- C-5 (also known as the 8 carbon) hydroxyl group of D-gluconate In the synthesis and metabolism of carbohydrates, Monosaccharides Are Reducing Agents e intermediates are very often not the sugars them selves but their phosphorylated derivatives. Condensation Monosaccharides can be oxidized by relative of phosphoric acid with one of the hydroxyl groups of a mild oxidizing agents such as ferric (Fe +)or sugar forms a phosphate ester, as in glucose 6-phosphate cupric(Cu-v ion(Fig. 7-10a). The carbonyl carbon is (Fig. 7-9). Sugar phosphates are relatively stable at neu- oxidized to a carboxyl group. Glucose and other sugars tral pH and bear a negative charge. One effect of sugar capable of reducing ferric or cupric ion are called re phosphorylation within cells is to trap the sugar inside the ducing sugars. This property is the basis of fehlings cell; most cells do not have plasma membrane trans- reaction, a qualitative test for the presence of reducing porters for phosphorylated sugars. Phosphorylation also sugar. By measuring the amount of oxidizing agent re- activates sugars for subsequent chemical transformation. duced by a solution of a sugar, it is also possible to es- Several important phosphorylated derivatives of sugars timate the concentration of that sugar. For many years are components of nucleotides(discussed in the next this test was used to detect and measure elevated glu- chapter) cose levels in blood and urine in the diagnosis of dia
In the synthesis and metabolism of carbohydrates, the intermediates are very often not the sugars themselves but their phosphorylated derivatives. Condensation of phosphoric acid with one of the hydroxyl groups of a sugar forms a phosphate ester, as in glucose 6-phosphate (Fig. 7–9). Sugar phosphates are relatively stable at neutral pH and bear a negative charge. One effect of sugar phosphorylation within cells is to trap the sugar inside the cell; most cells do not have plasma membrane transporters for phosphorylated sugars. Phosphorylation also activates sugars for subsequent chemical transformation. Several important phosphorylated derivatives of sugars are components of nucleotides (discussed in the next chapter). Monosaccharides Are Reducing Agents Monosaccharides can be oxidized by relatively mild oxidizing agents such as ferric (Fe3) or cupric (Cu2) ion (Fig. 7–10a). The carbonyl carbon is oxidized to a carboxyl group. Glucose and other sugars capable of reducing ferric or cupric ion are called reducing sugars. This property is the basis of Fehling’s reaction, a qualitative test for the presence of reducing sugar. By measuring the amount of oxidizing agent reduced by a solution of a sugar, it is also possible to estimate the concentration of that sugar. For many years this test was used to detect and measure elevated glucose levels in blood and urine in the diagnosis of dia- 244 Part I Structure and Catalysis CH2OH H O HO NH C PO3 N-Acetylmuramic acid R H OH H H H CH2 OH H HO D-Glucono--lactone OH H OH H H CH2OH H O HO NH2 -D-Mannosamine H OH H H H CH2OH H O OH HO OH H OH H H H H2N H O OH H OH H H H O CH3 -D-Glucose Muramic acid CH2OH H O OH HO NH C glucosamine H OH H H H O CH3 R Glucose family H OH HO -L-Rhamnose OH H OH H H O C O O C OH H HO -D-Glucuronate OH H OH H H H O O CH2OH CH2OH H N-Acetylneuraminic acid (a sialic acid) OH H O O -D-Glucosamine CH2OH H O OH HO NH2 H OH H H H -D-Galactosamine CH2OH H O OH HO CH3 H OH H H H CH2OH HO R O O O H H HO -D-Glucose 6-phosphate OH H OH H OH H O NH2 OH H HO -L-Fucose OH H OH H H H O CH3 H Amino sugars Acidic sugars Deoxy sugars O OH CH2OH H HO D-Gluconate OH H H H C OH H HN CH3 C O R H H 2 N-Acetyl--D- C OH H H OH C O COO O C H CH3 R FIGURE 7–9 Some hexose derivatives important in biology. In amino sugars, an ONH2 group replaces one of the OOH groups in the parent hexose. Substitution of OH for OOH produces a deoxy sugar; note that the deoxy sugars shown here occur in nature as the L isomers. The acidic sugars contain a carboxylate group, which confers a negative charge at neutral pH. D-Glucono--lactone results from formation of an ester linkage between the C-1 carboxylate group and the C-5 (also known as the carbon) hydroxyl group of D-gluconate. 8885d_c07_238-272 11/21/03 7:38 AM Page 244 Mac113 mac113:122_EDL:
885c07-238-27211/21/037:38 AM Page245Mac113mac11:4EDL FIGURE 7-10 Sugars as reducing agents. (a)Oxidation of the H carbon of glucose and other sugars is the basis for 1*) produced under alkalin conditions forms a red cuprous oxide precipitate. In the hem HoH H-C-OH acetal (ring)form, C-1 of glucose cannot be oxidized by Cu2+. owever, the open-chain form is in equilibrium with the ring H-c-oh 2Cu 2CuH-c-oh m,and eventually the oxidation reaction goes to completion The reaction with Cu2+ is not as simple as the equation here H-C-OH implies; in addition to D-gluconate, a number of shorter-chain H OH CH,OH CH,OH acids are produced by the fragmentation of glucose. (b) D-Gl glucose concentration is commonly determined by measuring the amount of H2O2 produced in the reaction catalyzed by glucose oxidase. In the reaction mixture, a second enzyme, peroxidase, talyzes reaction of the H2O2 with a colorless compound to oxidase, D- Glucono-& -Lactone+Ho produce a colored compound, the amount of which is then measured spectrophotometrically. betes mellitus. Now. more sensitive methods for meas- To name reducing disaccharides such as maltose un uring blood glucose employ an enzyme, glucose oxidase ambiguously, and especially to name more complex Fig.7-10b).■ oligosaccharides, several rules are followed By conven- tion, the name describes the compound with its nonre- Disaccharides Contain a Glycosidic Bond ducing end to the left, and we can"build up"the name Disaccharides(such as maltose, lactose, and sucrose) in the following order. (1) Give the configuration (a or consist of two monosaccharides joined covalently by an B) at the anomeric carbon joining the first O-glycosidie bond, which is formed when a hydroxy charide unit (on the left) to the second. (2) Name the group of one sugar reacts with the anomeric carbon of the other(Fig. 7-11). This reaction represents the for- mation of an acetal from a hemiacetal(such as glu- CH,OH CH,OH copyranose) and an alcohol (a hydroxyl group of the second sugar molecule)(Fig. 7-5). Glycosidic bonds are readily hydrolyzed by acid but resist cleavage by base H、oHH Thus disaccharides can be hydrolyzed to yield their free monosaccharide components by boiling with dilute acid OH H OH N-glycosyl bonds join the anomeric carbon of a sugar to aD-Glucose a nitrogen atom in glycoproteins(see Fig 7-31) and nu- cleotides(see Fig 8-1) The oxidation of a sugar's anomeric carbon by cupric or ferric ion(the reaction that defines a reduc- HOOH 6CH2OH ng sugar) occurs only with the linear form, which ex- ists in equilibrium with the cyclic form(S). When the anomeric carbon is involved in a glycosidic bond, that OH H OH H sugar residue cannot take the linear form and therefore becomes a nonreducing sugar. In describing disaccha rides or polysaccharides, the end of a chain with a free Maltose anomeric carbon (one not involved in a glycosidic bond) ae-D-glucopyranosyl-(1-4)-D-glucopyranose is commonly called the reducing end. FIGURE 7-11 Formation of maltose. a disaccharide is formed from The disaccharide maltose (ig. 7-11)contains two two monosaccharides there, two molecules of D-glucose) when an D-glucose residues joined by a glycosidic linkage be--OH (alcohol) of one glucose molecule (right)condenses with the tween C-1(the anomeric carbon) of one glucose residue intramolecular hemiacetal of the other glucose molecule (left), with and C-4 of the other. Because the disaccharide retains elimination of H,o and formation of an O-glycosidic bond. The re- a free anomeric carbon(C-1 of the glucose residue on versal of this reaction is hydrolysis-attack by H2O on the glycoside the right in Fig. 7-11), maltose is a reducing sugar. The bond. The maltose molecule retains a reducing hemiacetal at the configuration of the anomeric carbon atom in the gly- C-1 not involved in the glycosidic bond. Because mutarotation inter- cosidic linkage is a. The glucose residue with the free converts the a and B forms of the hemiacetal, the bonds at this posi anomeric carbon is capable of existing in a-and B-pyra- tion are sometimes depicted with wavy lines, as shown here, to indi- nose forms cate that the structure may be either a or B
betes mellitus. Now, more sensitive methods for measuring blood glucose employ an enzyme, glucose oxidase (Fig. 7–10b). ■ Disaccharides Contain a Glycosidic Bond Disaccharides (such as maltose, lactose, and sucrose) consist of two monosaccharides joined covalently by an O-glycosidic bond, which is formed when a hydroxyl group of one sugar reacts with the anomeric carbon of the other (Fig. 7–11). This reaction represents the formation of an acetal from a hemiacetal (such as glucopyranose) and an alcohol (a hydroxyl group of the second sugar molecule) (Fig. 7–5). Glycosidic bonds are readily hydrolyzed by acid but resist cleavage by base. Thus disaccharides can be hydrolyzed to yield their free monosaccharide components by boiling with dilute acid. N-glycosyl bonds join the anomeric carbon of a sugar to a nitrogen atom in glycoproteins (see Fig. 7–31) and nucleotides (see Fig. 8–1). The oxidation of a sugar’s anomeric carbon by cupric or ferric ion (the reaction that defines a reducing sugar) occurs only with the linear form, which exists in equilibrium with the cyclic form(s). When the anomeric carbon is involved in a glycosidic bond, that sugar residue cannot take the linear form and therefore becomes a nonreducing sugar. In describing disaccharides or polysaccharides, the end of a chain with a free anomeric carbon (one not involved in a glycosidic bond) is commonly called the reducing end. The disaccharide maltose (Fig. 7–11) contains two D-glucose residues joined by a glycosidic linkage between C-1 (the anomeric carbon) of one glucose residue and C-4 of the other. Because the disaccharide retains a free anomeric carbon (C-1 of the glucose residue on the right in Fig. 7–11), maltose is a reducing sugar. The configuration of the anomeric carbon atom in the glycosidic linkage is . The glucose residue with the free anomeric carbon is capable of existing in - and -pyranose forms. To name reducing disaccharides such as maltose unambiguously, and especially to name more complex oligosaccharides, several rules are followed. By convention, the name describes the compound with its nonreducing end to the left, and we can “build up” the name in the following order. (1) Give the configuration ( or ) at the anomeric carbon joining the first monosaccharide unit (on the left) to the second. (2) Name the Chapter 7 Carbohydrates and Glycobiology 245 D-Glucose O2 glucose oxidase D-Glucono--lactone H2O2 CH2OH HO C O H OH 6 1 A G J A O O A A A O O O O O O O C C C C OH OH H H H 2 3 4 5 CH2OH HO C O H OH A G J A O O A A A O O O O O O H C C C C OH OH H H H D-Glucose (linear form) D-Gluconate (a) -D-Glucose 3 5 6 4 1 2 H OH OH H H H CH2OH O H OH HO 2Cu 2Cu2 H OH OH H H H CH2OH O H OH alcohol H2O Maltose -D-glucopyranosyl-(1n4)-D-glucopyranose H OH OH H H H CH2OH O H HO OH -D-Glucose condensation acetal hydrolysis H2O 3 5 6 4 1 2 H OH OH H CH2OH O H OH HO 3 5 6 4 1 2 H OH OH H H CH2OH O H H H H O -D-Glucose hemiaceta hemiacetal O H FIGURE 7–10 Sugars as reducing agents. (a) Oxidation of the anomeric carbon of glucose and other sugars is the basis for Fehling’s reaction. The cuprous ion (Cu) produced under alkaline conditions forms a red cuprous oxide precipitate. In the hemiacetal (ring) form, C-1 of glucose cannot be oxidized by Cu2. However, the open-chain form is in equilibrium with the ring form, and eventually the oxidation reaction goes to completion. The reaction with Cu2 is not as simple as the equation here implies; in addition to D-gluconate, a number of shorter-chain acids are produced by the fragmentation of glucose. (b) Blood glucose concentration is commonly determined by measuring the amount of H2O2 produced in the reaction catalyzed by glucose oxidase. In the reaction mixture, a second enzyme, peroxidase, catalyzes reaction of the H2O2 with a colorless compound to produce a colored compound, the amount of which is then measured spectrophotometrically. FIGURE 7–11 Formation of maltose. A disaccharide is formed from two monosaccharides (here, two molecules of D-glucose) when an OOH (alcohol) of one glucose molecule (right) condenses with the intramolecular hemiacetal of the other glucose molecule (left), with elimination of H2O and formation of an O-glycosidic bond. The reversal of this reaction is hydrolysis—attack by H2O on the glycosidic bond. The maltose molecule retains a reducing hemiacetal at the C-1 not involved in the glycosidic bond. Because mutarotation interconverts the and forms of the hemiacetal, the bonds at this position are sometimes depicted with wavy lines, as shown here, to indicate that the structure may be either or . (a) (b) 8885d_c07_238-272 11/21/03 7:38 AM Page 245 Mac113 mac113:122_EDL:
885d_c07-238-27211/21/037:38 AM Page246Mac113mac113:1aEDL 246 Part I Structure and Catalysis nonreducing residue; to distinguish five- and six-mem- many plants it is the principal form in which sugar is bered ring structures, insert"furano"or "pyrano"into transported from the leaves to other parts of the plant the name. B)Indicate in parentheses the two carbon body. Trehalose, Glc(alelaGlc(Fig 7-12)-a disac atoms joined by the glycosidic bond, with an arrow con- charide of D-glucose that, like sucrose, is a nonreducing necting the two numbers; for example, (1-4)shows sugar--is a major constituent of the circulating fluid that C-1 of the first-named sugar residue is joined to (hemolymph) of insects, serving as an energy-storage C-4 of the second. (4) Name the second residue. If there compound is a third residue, describe the second glycosidic bond by the same conventions. (To shorten the description CH2O CH2OH of complex polysaccharides, three-letter abbreviations for the monosaccharides are often used, as given in Table 7-1. Following this convention for naming oligosaccharides, maltose is a-D-glucopyranosyl-(1-4) D-glucopyranose. Because most sugars encountered in this book are the d enantiomers and the pyranose form Lactose(B form) of hexoses predominates, we generally use a shortened B-D-galactopyranosyl-(1-4)-B-D-glucopyranose version of the formal name of such compounds, giving Ga(B1→4)Glc the configuration of the anomeric carbon and naming the carbons joined by the glycosidic bond. In this ab- CH.OHI breviated nomenclature, maltose is Glc(a1-4)Glc. The disaccharide lactose (Fig. 7-12), which yields BRH HO D-galactose and D-glucose on hydrolysis, occurs natu- loHI rally only in milk. The anomeric carbon of the glucose residue is available for oxidation. and thus lactose is a reducing disaccharide. Its abbreviated name is a-D-glucopyranosyl B-D-fructofuranoside Gal(Bl-4)Glc. Sucrose(table sugar)is a disaccharide Glc(a1+2B)Fru of glucose and fructose. It is formed by plants but not by animals. In contrast to maltose and lactose, sucrose CH2OH contains no free anomeric carbon atom. the anomeric carbons of both monosaccharide units are involved in H the glycosidic bond(Fig. 7-12). Sucrose is therefore a HO nonreducing sugar. Nonreducing disaccharides are named as glycosides; in this case, the positions joined are the anomeric carbons. In the abbreviated nomen- clature, a double-headed arrow connects the symbols ucopyra Glda1-1aGlc specifying the anomeric carbons and their configura- tions. For example, the abbreviated name of sucrose FIGURE 7-12 Some common disaccharides. Like maltose in Figure is either Gle(al+2B)Fru or Fru(B26laGlc Sucrose 7-11, these are shown as Haworth perspectives. The common name, is a major intermediate product of photosynthesis; in full systematic name, and abbreviation are given for each disaccharide TABLE 7-1 Abbreviations for common monosaccharides and some of their derivatives Abequose Glucuronic acid GIcA Galactosamine Glucosamine N-Acetylgalactosamine N-Acetylglucosamine GICNAc Iduronic acid Mannose Muramic acid Rhamnose N-Acetylmuramic acid Mur2Ac N-Acetylneuraminic acid Neu5Ac Xylose (a sialic acid)
nonreducing residue; to distinguish five- and six-membered ring structures, insert “furano” or “pyrano” into the name. (3) Indicate in parentheses the two carbon atoms joined by the glycosidic bond, with an arrow connecting the two numbers; for example, (1n4) shows that C-1 of the first-named sugar residue is joined to C-4 of the second. (4) Name the second residue. If there is a third residue, describe the second glycosidic bond by the same conventions. (To shorten the description of complex polysaccharides, three-letter abbreviations for the monosaccharides are often used, as given in Table 7–1.) Following this convention for naming oligosaccharides, maltose is -D-glucopyranosyl-(1n4)- D-glucopyranose. Because most sugars encountered in this book are the D enantiomers and the pyranose form of hexoses predominates, we generally use a shortened version of the formal name of such compounds, giving the configuration of the anomeric carbon and naming the carbons joined by the glycosidic bond. In this abbreviated nomenclature, maltose is Glc(1n4)Glc. The disaccharide lactose (Fig. 7–12), which yields D-galactose and D-glucose on hydrolysis, occurs naturally only in milk. The anomeric carbon of the glucose residue is available for oxidation, and thus lactose is a reducing disaccharide. Its abbreviated name is Gal(1n4)Glc. Sucrose (table sugar) is a disaccharide of glucose and fructose. It is formed by plants but not by animals. In contrast to maltose and lactose, sucrose contains no free anomeric carbon atom; the anomeric carbons of both monosaccharide units are involved in the glycosidic bond (Fig. 7–12). Sucrose is therefore a nonreducing sugar. Nonreducing disaccharides are named as glycosides; in this case, the positions joined are the anomeric carbons. In the abbreviated nomenclature, a double-headed arrow connects the symbols specifying the anomeric carbons and their configurations. For example, the abbreviated name of sucrose is either Glc(1mn2)Fru or Fru(2mn1)Glc. Sucrose is a major intermediate product of photosynthesis; in many plants it is the principal form in which sugar is transported from the leaves to other parts of the plant body. Trehalose, Glc(1mn1)Glc (Fig. 7–12)—a disaccharide of D-glucose that, like sucrose, is a nonreducing sugar—is a major constituent of the circulating fluid (hemolymph) of insects, serving as an energy-storage compound. 246 Part I Structure and Catalysis Sucrose 4 5 1 2 H HOCH2 H HO HO 3 5 6 4 1 2 H OH OH H H CH2OH O H H O 6 Trehalose 3 5 1 4 2 H OH OH H O H OH HO 3 5 6 4 1 2 H OH OH H H CH2OH O H H H H O 6 -D-glucopyranosyl -D-glucopyranoside O OH H CH2OH 3 Glc( 1nn1 )Glc -D-glucopyranosyl - D-fructofuranoside Lactose ( form) 3 5 4 1 2 H OH OH H CH2OH O H HO OH 3 5 6 4 1 2 H OH OH H H CH2OH O H H H H O 6 -D-galactopyranosyl-(1n4)--D-glucopyranose Gal(1n4)Glc HOCH2 Glc(1nn 2)Fru FIGURE 7–12 Some common disaccharides. Like maltose in Figure 7–11, these are shown as Haworth perspectives. The common name, full systematic name, and abbreviation are given for each disaccharide. Abequose Abe Glucuronic acid GlcA Arabinose Ara Galactosamine GalN Fructose Fru Glucosamine GlcN Fucose Fuc N-Acetylgalactosamine GalNAc Galactose Gal N-Acetylglucosamine GlcNAc Glucose Glc Iduronic acid IdoA Mannose Man Muramic acid Mur Rhamnose Rha N-Acetylmuramic acid Mur2Ac Ribose Rib N-Acetylneuraminic acid Neu5Ac Xylose Xyl (a sialic acid) TABLE 7–1 Abbreviations for Common Monosaccharides and Some of Their Derivatives 8885d_c07_238-272 11/21/03 7:38 AM Page 246 Mac113 mac113:122_EDL:
88607238-2721/21/037:38 AM Page247Mac113ac11:aEDL SUMMARY 7. 1 Monosaccharides and Disaccharides Homopolysaccharides Heteropolysaccharides Unbranched Branched Multiple a Sugars(also called saccharides) are compounds monol monomer containing an aldehyde or ketone group and types two or more hydroxyl groups a Monosaccharides generally contain several chiral carbons and therefore exist in a variety of stereochemical forms, which may be represented on paper as Fischer projections Epimers are sugars that differ in configuration at only one carbon atom. a Monosaccharides commonly form internal hemiacetals or hemiketals. in which the aldehyde or ketone group joins with a hydroxyl group of the same molecule, creating a cyclic QrrrQ structure; this can be represented as a Haworth perspective formula. The carbon atom originally found in the aldehyde or ketone group(the anomeric carbon) can assume either of two configurations, a and B, which are FIGURE 7-13 Homo- and heteropolysaccharides. Polysaccharides form,which is in equilibrium with the cyclized in straight or branched chains of varying lengen t monosaccharides interconvertible by mutarotation. In the linear ay be composed of one, two, or several differe forms, the anomeric carbon is easily oxidized I A hydroxyl group of one monosaccharide can for example) serve as structural elements in plant cell add to the anomeric carbon of a second walls and animal exoskeletons. Heteropolysaccharides monosaccharide to form an acetal. in this provide extracellular support for organisms of all king disaccharide, the glycosidic bond protects the doms. For example, the rigid layer of the bacterial cell anomeric carbon from oxidation envelope(the peptidoglycan) is composed in part of a a Oligosaccharides are short polymers of several heteropolysaccharide built from two alternating mond monosaccharides joined by glycosidic bonds. At saccharide units. In animal tissues, the extracellular one end of the chain, the reducing end, is a space is occupied by several types of heteropolysac- monosaccharide unit whose anomeric carbon is charides, which form a matrix that holds individual cells not involved in a glycosidic bond together and provides protection, shape, and support to cells, tissues, and organs a The common nomenclature for di-or Unlike proteins, polysaccharides generally do not oligosaccharides specifies the order of have definite molecular weights. This difference is a con- monosaccharide units, the configuration at sequence of the mechanisms of assembly of the two each anomeric carbon and the carbon atoms types of polymers. As we shall see in Chapter 27, pro involved in the glycosidic linkage(s) teins are synthesized on a template(messenger RNA) of defined sequence and length, by enzymes that follow the template exactly For polysaccharide synthesis there 7.2 Polysaccharides is no template; rather, the program for polysaccharide Most carbohydrates found in nature occur as polysac- synthesis is intrinsic to the enzymes that catalyze the charides, polymers of medium to high molecular weight. polymerization of the monomeric units, and there is no Polysaccharides, also called glycans, differ from each pecific stopping point in the synthetic process other in the identity of their recurring monosaccharide units, in the length of their chains, in the types of bonds Some Homopolysaccharide Are Stored Forms of Fuel linking the units, and in the degree of branching. Homo- The most important storage polysaccharides are starch polysaccharides contain only a single type of monomer; in plant cells and glycogen in animal cells. Both poly heteropolysaccharides contain two or more different saccharides occur intracellularly as large clusters or kinds(Fig. 7-13). Some homopolysaccharide serve as granules (Fig. 7-14). Starch and glycogen molecules are storage forms of monosaccharides that are used as fuels; heavily hydrated, because they have many exposed hy- starch and glycogen are homopolysaccharide of this droxyl groups available to hydrogen-bond with water. type. Other homopolysaccharide(cellulose and chitin, Most plant cells have the ability to form starch, but it is
SUMMARY 7.1 Monosaccharides and Disaccharides ■ Sugars (also called saccharides) are compounds containing an aldehyde or ketone group and two or more hydroxyl groups. ■ Monosaccharides generally contain several chiral carbons and therefore exist in a variety of stereochemical forms, which may be represented on paper as Fischer projections. Epimers are sugars that differ in configuration at only one carbon atom. ■ Monosaccharides commonly form internal hemiacetals or hemiketals, in which the aldehyde or ketone group joins with a hydroxyl group of the same molecule, creating a cyclic structure; this can be represented as a Haworth perspective formula. The carbon atom originally found in the aldehyde or ketone group (the anomeric carbon) can assume either of two configurations, and , which are interconvertible by mutarotation. In the linear form, which is in equilibrium with the cyclized forms, the anomeric carbon is easily oxidized. ■ A hydroxyl group of one monosaccharide can add to the anomeric carbon of a second monosaccharide to form an acetal. In this disaccharide, the glycosidic bond protects the anomeric carbon from oxidation. ■ Oligosaccharides are short polymers of several monosaccharides joined by glycosidic bonds. At one end of the chain, the reducing end, is a monosaccharide unit whose anomeric carbon is not involved in a glycosidic bond. ■ The common nomenclature for di- or oligosaccharides specifies the order of monosaccharide units, the configuration at each anomeric carbon, and the carbon atoms involved in the glycosidic linkage(s). 7.2 Polysaccharides Most carbohydrates found in nature occur as polysaccharides, polymers of medium to high molecular weight. Polysaccharides, also called glycans, differ from each other in the identity of their recurring monosaccharide units, in the length of their chains, in the types of bonds linking the units, and in the degree of branching. Homopolysaccharides contain only a single type of monomer; heteropolysaccharides contain two or more different kinds (Fig. 7–13). Some homopolysaccharides serve as storage forms of monosaccharides that are used as fuels; starch and glycogen are homopolysaccharides of this type. Other homopolysaccharides (cellulose and chitin, for example) serve as structural elements in plant cell walls and animal exoskeletons. Heteropolysaccharides provide extracellular support for organisms of all kingdoms. For example, the rigid layer of the bacterial cell envelope (the peptidoglycan) is composed in part of a heteropolysaccharide built from two alternating monosaccharide units. In animal tissues, the extracellular space is occupied by several types of heteropolysaccharides, which form a matrix that holds individual cells together and provides protection, shape, and support to cells, tissues, and organs. Unlike proteins, polysaccharides generally do not have definite molecular weights. This difference is a consequence of the mechanisms of assembly of the two types of polymers. As we shall see in Chapter 27, proteins are synthesized on a template (messenger RNA) of defined sequence and length, by enzymes that follow the template exactly. For polysaccharide synthesis there is no template; rather, the program for polysaccharide synthesis is intrinsic to the enzymes that catalyze the polymerization of the monomeric units, and there is no specific stopping point in the synthetic process. Some Homopolysaccharides Are Stored Forms of Fuel The most important storage polysaccharides are starch in plant cells and glycogen in animal cells. Both polysaccharides occur intracellularly as large clusters or granules (Fig. 7–14). Starch and glycogen molecules are heavily hydrated, because they have many exposed hydroxyl groups available to hydrogen-bond with water. Most plant cells have the ability to form starch, but it is Chapter 7 Carbohydrates and Glycobiology 247 Homopolysaccharides Unbranched Branched Heteropolysaccharides Two monomer types, unbranched Multiple monomer types, branched FIGURE 7–13 Homo- and heteropolysaccharides. Polysaccharides may be composed of one, two, or several different monosaccharides, in straight or branched chains of varying length. 8885d_c07_238-272 11/21/03 7:38 AM Page 247 Mac113 mac113:122_EDL:
