1. 7 | Carbohydrates and Glycobiology
© 2017 W. H. Freeman and Company

2. Carbohydrates are the most abundant biological molecule.
Energy storage
Structural materials
and more….
Carbohydrates are the most abundant biological molecule.
(C·H2O)n (n≥3)
Chapter 8 Opener

3. Carbohydrates Named so because many have formula Cn(H2O)n
Produced from CO2 and H2O via photosynthesis in plants
Range from as small as glyceraldehyde (Mw = 90 g/mol) to as large as amylopectin (Mw > 200,000,000 g/mol)
Fulfill a variety of functions, including:
energy source and energy storage
structural component of cell walls and exoskeletons
informational molecules in cell-cell signaling
Can be covalently linked with proteins and lipids

4. Carbohydrates Basic nomenclature: Common functional groups:
number of carbon atoms in the carbohydrate + -ose
example: three carbons = triose
Common functional groups:
All carbohydrates initially had a carbonyl functional group.
aldehydes = aldose
ketones = ketose

5. Carbohydrates Can Be Constitutional Isomers
An aldose is a carbohydrate with aldehyde functionality.
A ketose is a carbohydrate with ketone functionality.
FIGURE 7-1a Representative monosaccharides. (a)Two trioses, an aldose and a ketose. The carbonyl group in each is shaded.

6. Enantiomers Are Mirror Images
FIGURE 7–2 (part 1) Three ways to represent the two enantiomers of glyceraldehyde. The enantiomers are mirror images of each other. Ball-and-stick models show the actual configuration of molecules. Recall (see Fig. 1–18) that in perspective formulas, the wide end of a solid wedge projects out of the plane of the paper, toward the reader; a dashed wedge extends behind.

7. Carbohydrates Can Be Stereoisomers
Enantiomers
stereoisomers that are nonsuperimposable mirror images
In sugars that contain many chiral centers, only the one that is most distant from the carbonyl carbon is designated as d (right) or l (left).
d and l isomers of a sugar are enantiomers.
For example, l- and d-glucose have the same water solubility.
Most hexoses in living organisms are d stereoisomers.
Some simple sugars occur in the l form, such as l-arabinose.

8. Drawing Monosaccharides
Chiral compounds can be drawn using perspective formulas.
However, chiral carbohydrates are usually represented by Fischer projections.
Horizontal bonds are pointing toward you; vertical bonds are projecting away from you.
FIGURE 7-2 (part 2) Three ways to represent the two enantiomers of glyceraldehyde. The enantiomers are mirror images of each other. Ball-and-stick models show the actual configuration of molecules. Recall (see Fig. 1–18) that in perspective formulas, the wide end of a solid wedge projects out of the plane of the paper, toward the reader; a dashed wedge extends behind. FIGURE 7-2 (part 3) Three ways to represent the two enantiomers of glyceraldehyde. The enantiomers are mirror images of each other. Ball-and-stick models show the actual configuration of molecules. Recall (see Fig. 1–18) that in perspective formulas, the wide end of a solid wedge projects out of the plane of the paper, toward the reader; a dashed wedge extends behind.

9. Carbohydrates Can Be Stereoisomers
Epimers are stereoisomers that differ at only one chiral center.
Epimers are NOT mirror images, and therefore are NOT enantiomers.
Epimers are diastereomers; diastereomers have different physical properties (i.e., water solubility, melting temp).
example: d-Threose is the C-2 epimer of d-erythrose.
Both are d sugars because they both have the same orientation around the last chiral carbon in the chain.

10. Diastereomers Diastereomers: stereoisomers that are not mirror images
Diastereomers have different physical properties.
For example, water solubilities of threose and erythrose are different.
FIGURE 7–3a (part 1) 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.

11. Epimers d-Mannose and d-galactose are both epimers of d-glucose.
d-Mannose and d-galactose vary at more than one chiral center and are diastereomers, but not epimers.
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 light red or blue).

12. Common Carbohydrates in Biochemistry
Ribose is the standard five-carbon sugar.
Glucose is the standard six-carbon sugar.
Galactose is an epimer of glucose.
Mannose is an epimer of glucose.
Fructose is the ketose form of glucose.

13. FIGURE 7–3a (part 1) Aldoses and ketoses
FIGURE 7–3a (part 1) 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.

14. FIGURE 7-3a (part 2) Aldoses and ketoses
FIGURE 7-3a (part 2) 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.

15. FIGURE 7-3a (part 3) Aldoses and ketoses
FIGURE 7-3a (part 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.

16. The D-aldoses with up to six carbon atoms
D sugars have the same
absolute configuration at the
asymmetric center farthest
from their carbonyl group.
Figure 8-1

17. D sugars 2n-2 possible stereoisomers L sugars CHO HOCH CH2OH HCOH
L-Erythrose
L-Threose
2n-2 possible
stereoisomers
Here, n = 4, so there are 4 stereoisomers
L sugars
Figure 8-1 part 1

18. Ribose is the most common aldo-pentose
Figure 8-1 part 2

19. Glucose and mannose are “epimers”, as they differ by at only one chiral center.
Figure 8-1 part 3

20. Carbon atom number in D-glucose:
2n-2 possible
stereoisomers,
as C1 and C6 are not chiral centers.
Page 221

21. The D-ketoses up to six carbon atoms
Only 2n-3 possible stereoisomers,
as there is one less stereo center
as compared to the aldoses.
Figure 8-2

22. These ketoses will be seen again when we cover to metabolism.
Figure 8-2

23. Reactivity of Carbohydrates: Hemiacetals and Hemiketals
Aldehyde and ketone carbons are electrophilic.
Alcohol oxygen atom is nucleophilic.
When aldehydes are attacked by alcohols, hemiacetals form.
When ketones are attacked by alcohols, hemiketals form.
These reactions form the basis of cyclization of sugars.
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. 252).

24. Be sure to know this!
Page 221

25. Cyclization of Monosaccharides
The nucleophilic alcohol attacks the electrophilic carbonyl carbon, allowing formation of a hemiacetal.
As a result, the linear carbohydrate forms a ring structure.
At the completion of this structure, the carbonyl carbon is reduced to an alcohol
The orientation of the alcohol around the carbon is variable and transient.
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 α and β anomers, which differ only in the stereochemistry around the hemiacetal carbon. This reaction is reversible. The interconversion of α and β anomers is called mutarotation.

26. The interconversion of D-glucopyranose between its a and b forms.
C1 is the called anomeric carbon, hence, each sugar has two “anomers”, the a and b anomers.
Figure 8-4

27. Cyclization of Monosaccharides
Pentoses and hexoses readily undergo intramolecular cyclization.
The former carbonyl carbon becomes a new chiral center, called the anomeric carbon.
When the former carbonyl oxygen becomes a hydroxyl group, the position of this group determines if the anomer is  or .
If the hydroxyl group is on the opposite side (trans) of the ring as the CH2OH moiety, the configuration is .
If the hydroxyl group is on the same side (cis) of the ring as the CH2OH moiety, the configuration is .

28. Cyclization of Monosaccharides: Pyranoses and Furanoses
Six-membered oxygen-containing rings are called pyranoses after the pyran ring structure.
Five-membered oxygen-containing rings are called furanoses after the furan ring structure.
The anomeric carbon is usually drawn on the right side.
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 shown for comparison.

29. FIGURE 7–7 Pyranoses and furanoses
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 shown for comparison.

30. Conformational Formulas of Cyclized Monosaccharides
Cyclohexane rings have “chair” or “boat” conformations.
Pyranose rings favor “chair” conformations.
Multiple “chair” conformations are possible but require energy for interconversion (~46 kJ/mole).
FIGURE 78 Conformational formulas of pyranoses. (a) Two chair forms of the pyranose ring of β-D-glucopyranose. Two conformers such as these are not readily interconvertible; an input of about 46 kJ of energy per mole of sugar is required to force the interconversion of chair forms. Another conformation, the “boat” (not shown), is seen only in derivatives with very bulky substituents.

31. Two chair conformation of b-D-glucopyranose
Less crowding with bulky OH and CH2OH groups in the equitorial positions
More crowding with bulky OH and CH2OH groups in the axial positions
Dominant form in solution.
Only b-D-glucose can simultaneously have all five non-H substituents in equatorial positions.
Figure 8-5

32. Important Hexose Derivatives
FIGURE 7-9 Some hexose derivatives important in biology. In amino sugars, an —NH2 group replaces one of the —OH groups in the parent hexose. Substitution of —H for —OH 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-δ-lactone results from formation of an ester linkage between the C-1 carboxylate group and the C-5 (also known as the δ carbon) hydroxyl group of D-gluconate.

33. Often seen along with table sugar:
Box 8-2a

34. Also seen at the table, and in diet sodas:
Box 8-2b

35. Sometimes used with aspartame, acts synergistically to make both compounds sweeter.
Box 8-2c

36. Still room for improvement…
Since 1879
Carcinogen ?
Since 1981
Causes cancer in rats in VERY high dosages.
(problem for phenylketonuria)

37. Reducing Sugars Reducing sugars have a free anomeric carbon.
Aldehyde can reduce Cu2+ to Cu+ (Fehling’s test).
Aldehyde can reduce Ag+ to Ag0 (Tollens’ test).
It allows detection of reducing sugars, such as glucose.
Modern detection techniques use colorimetric and electrochemical tests.

38. Colorimetric Glucose Analysis
Enzymatic methods are used to quantify reducing sugars such as glucose.
The enzyme glucose oxidase catalyzes the conversion of glucose to glucono--lactone and hydrogen peroxide.
Hydrogen peroxide oxidizes organic molecules into highly colored compounds.
Concentrations of such compounds is measured colorimetrically.
Electrochemical detection is used in portable glucose sensors.

39. The Glycosidic Bond
Two sugar molecules can be joined via a glycosidic bond between an anomeric carbon and a hydroxyl carbon.
The glycosidic bond (an acetal) between monomers is more stable and less reactive than the hemiacetal at the second monomer.
The second monomer, with the hemiacetal, is reducing.
The anomeric carbon involved in the glycosidic linkage is nonreducing.
Disacharides can be named by the organization and linkage or a common name.
The disaccharide formed upon condensation of two glucose molecules via a 1  4 bond is described as α-D-glucopyranosyl-(14)-D-glucopyranose.
The common name for this disaccharide is maltose.

40. FIGURE 7-10 Formation of maltose
FIGURE 7-10 Formation of maltose. A disaccharide is formed from two monosaccharides (here, two molecules of D-glucose) when an —OH (alcohol) of one glucose molecule (right) condenses with the intramolecular hemiacetal of the other glucose molecule (left), with elimination of H2O and formation of a glycosidic bond. The reversal of this reaction is hydrolysis—attack by H2O on the glycosidic bond. The maltose molecule, shown here as an illustration, retains a reducing hemiacetal at the C-1 not involved in the glycosidic bond. Because mutarotation interconverts the α and β 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 α or β.

41. Nonreducing Disaccharides
Two sugar molecules can be also joined via a glycosidic bond between two anomeric carbons.
The product has two acetal groups and no hemiacetals.
There are no reducing ends; this is a nonreducing sugar.
FIGURE 7-11 Two common disaccharides. Like maltose in Figure 7–10, these are shown as Haworth perspectives. The common name, full systematic name, and abbreviation are given for each disaccharide. Formal nomenclature for sucrose names glucose as the parent glycoside, although it is typically depicted as shown, with glucose on the left. The two abbreviated symbols shown for sucrose are equivalent ().

42. Polysaccharides Natural carbohydrates are usually found as polymers.
These polysaccharides can be:
homopolysaccharides (one monomer unit)
heteropolysaccharides (multiple monomer units)
linear (one type of glycosidic bond)
branched (multiple types of glycosidic bonds)
Polysaccharides do not have a defined molecular weight.
This is in contrast to proteins because, unlike proteins, no template is used to make polysaccharides.
Polysaccharides are often in a state of flux; monomer units are added and removed as needed by the organism.

43. FIGURE 7-12 Homo- and heteropolysaccharides
FIGURE 7-12 Homo- and heteropolysaccharides. Polysaccharides may be composed of one, two, or several different monosaccharides, in straight or branched chains of varying length.

44. Homopolymers of Glucose: Glycogen
Glycogen is a branched homopolysaccharide of glucose.
Glucose monomers form (1  4) linked chains.
There are branch points with (1  6) linkers every 8–12 residues.
Molecular weight reaches several millions.
It functions as the main storage polysaccharide in animals.

45. Homopolymers of Glucose: Starch
Starch is a mixture of two homopolysaccharides of glucose.
Amylose is an unbranched polymer of (1  4) linked residues.
Amylopectin is branched like glycogen, but the branch points with (1  6) linkers occur every 24–30 residues.
Molecular weight of amylopectin is up to 200 million.
Starch is the main storage polysaccharide in plants.

46. Glycosidic Linkages in Glycogen and Starch
FIGURE 7-13a,b Glycogen and starch. (a) A short segment of amylose, a linear polymer of D-glucose residues in (α1→4) linkage. A single chain can contain several thousand glucose residues. Amylopectin has stretches of similarly linked residues between branch points. Glycogen has the same basic structure, but has more branching than amylopectin. (b) An (α1→6) branch point of glycogen or amylopectin.

47. Mixture of Amylose and Amylopectin in Starch
FIGURE 7-13c Glycogen and starch. (c) A cluster of amylose and amylopectin like that believed to occur in starch granules. Strands of amylopectin (black) form double-helical structures with each other or with amylose strands (blue). Amylopectin has frequent (α16) branch points (red). Glucose residues at the nonreducing ends of the outer branches are removed enzymatically during the mobilization of starch for energy production. Glycogen has a similar structure but is more highly branched and more compact.

48. Metabolism of Glycogen and Starch
Glycogen and starch are insoluble due to their high molecular weight and often form granules in cells.
Granules contain enzymes that synthesize and degrade these polymers.
Glycogen and amylopectin have one reducing end but many nonreducing ends.
Enzymatic processing occurs simultaneously in many nonreducing ends.

49. Homopolymers of Glucose: Cellulose
Cellulose is a linear homopolysaccharide of glucose.
Glucose monomers form (1  4) linked chains.
Hydrogen bonds form between adjacent monomers.
There are additional H-bonds between chains.
Structure is tough and water insoluble.
It is the most abundant polysaccharide in nature.
Cotton is nearly pure fibrous cellulose.

50. Hydrogen Bonding in Cellulose
FIGURE 7-14 Cellulose. (a) Two units of a cellulose chain; the D-glucose residues are in (β1→4) linkage. The rigid chair structures can rotate relative to one another.

51. Cellulose Metabolism
The fibrous structure and water insolubility make cellulose a difficult substrate to act upon.
Most animals cannot use cellulose as a fuel source because they lack the enzyme to hydrolyze (1 4) linkages.
Fungi, bacteria, and protozoa secrete cellulase, which allows them to use wood as source of glucose.
Ruminants and termites live symbiotically with microorganisms that produce cellulase and are able to absorb the freed glucose into their bloodstreams.
Cellulases hold promise in the fermentation of biomass into biofuels.

52. Q: What do these two have in common?
A: They both have a “sugary” shell
80% sucrose
10% glucose
10% fructose
100% N-acetylglucosamine.
FIGURE 7-16b Chitin. (b) A spotted June beetle (Pelidnota punctata), showing its surface armor (exoskeleton) of chitin.

53. Chitin Is a Homopolysaccharide
Chitin is a linear homopolysaccharide of N-acetylglucosamine.
N-acetylglucosamine monomers form (1  4)-linked chains.
forms extended fibers that are similar to those of cellulose
hard, insoluble, cannot be digested by vertebrates
structure is tough but flexible, and water insoluble
found in cell walls in mushrooms and in exoskeletons of insects, spiders, crabs, and other arthropods
FIGURE 7-16a Chitin. (a) A short segment of chitin, a homopolymer of N-acetyl-D-glucosamine units in (β1→4) linkage.

54. Agar and Agarose
Agar is a branched heteropolysaccharide composed of agarose and agaropectin.
Agar serves as a component of cell wall in some seaweeds.
Agar solutions form gels that are commonly used in the laboratory as a surface for growing bacteria.
Agarose solutions form gels that are commonly used in the laboratory for separation DNA by electrophoresis.

55. Agarose Is a Heteropolysaccharide
FIGURE 7-21 Agarose. The repeating unit consists of D-galactose (β1→4)-linked to 3,6-anhydro-L-galactose (in which an ether bridge connects C-3 and C-6). These units are joined by (α1→3) glycosidic links to form a polymer 600 to 700 residues long. A small fraction of the 3,6-anhydrogalactose residues have a sulfate ester at C-2 (as shown here). The open parentheses in the systematic name indicate that the repeating unit extends from both ends.

56. Glycosaminoglycans Linear polymers of repeating disaccharide units
One monomer is either:
N-acetyl-glucosamine or
N-acetyl-galactosamine
Negatively charged
uronic acids (C6 oxidation)
sulfate esters
Extended hydrated molecule
minimizes charge repulsion
Forms meshwork with fibrous proteins to form extracellular matrix
connective tissue
lubrication of joints

57. FIGURE 7–22 (part 1a) Repeating units of some common glycosaminoglycans of extracellular matrix. The molecules are copolymers of alternating uronic acid and amino sugar residues (keratan sulfate is the exception), with sulfate esters in any of several positions, except in hyaluronan. The ionized carboxylate and sulfate groups (red in the perspective formulas) give these polymers their characteristic high negative charge. Therapeutic heparin contains primarily iduronic acid (IdoA) and a smaller proportion of glucuronic acid (GlcA, not shown), and is generally highly sulfated and heterogeneous in length. The space-filling model shows a heparin segment as its solution structure, as determined by NMR spectroscopy (PDB ID 1HPN). The carbons in the iduronic acid sulfate are colored blue; those in glucosamine sulfate are green. Oxygen and sulfur atoms are shown in their standard colors of red and yellow, respectively. The hydrogen atoms are not shown (for clarity). Heparan sulfate (not shown) is similar to heparin but has a higher proportion of GlcA and fewer sulfate groups, arranged in a less regular pattern.

58. FIGURE 7-22 (part 1b) Repeating units of some common glycosaminoglycans of extracellular matrix. The molecules are copolymers of alternating uronic acid and amino sugar residues (keratan sulfate is the exception), with sulfate esters in any of several positions, except in hyaluronan. The ionized carboxylate and sulfate groups (red in the perspective formulas) give these polymers their characteristic high negative charge. Therapeutic heparin contains primarily iduronic acid (IdoA) and a smaller proportion of glucuronic acid (GlcA, not shown), and is generally highly sulfated and heterogeneous in length. The space-filling model shows a heparin segment as its solution structure, as determined by NMR spectroscopy (PDB ID 1HPN). The carbons in the iduronic acid sulfate are colored blue; those in glucosamine sulfate are green. Oxygen and sulfur atoms are shown in their standard colors of red and yellow, respectively. The hydrogen atoms are not shown (for clarity). Heparan sulfate (not shown) is similar to heparin but has a higher proportion of GlcA and fewer sulfate groups, arranged in a less regular pattern.

59. FIGURE 7-22 (part 2) Repeating units of some common glycosaminoglycans of extracellular matrix. The molecules are copolymers of alternating uronic acid and amino sugar residues (keratan sulfate is the exception), with sulfate esters in any of several positions, except in hyaluronan. The ionized carboxylate and sulfate groups (red in the perspective formulas) give these polymers their characteristic high negative charge. Therapeutic heparin contains primarily iduronic acid (IdoA) and a smaller proportion of glucuronic acid (GlcA, not shown), and is generally highly sulfated and heterogeneous in length. The space-filling model shows a heparin segment as its solution structure, as determined by NMR spectroscopy (PDB ID 1HPN). The carbons in the iduronic acid sulfate are colored blue; those in glucosamine sulfate are green. Oxygen and sulfur atoms are shown in their standard colors of red and yellow, respectively. The hydrogen atoms are not shown (for clarity). Heparan sulfate (not shown) is similar to heparin but has a higher proportion of GlcA and fewer sulfate groups, arranged in a less regular pattern.

60. Heparin and Heparan Sulfate
Heparin is linear polymer, 3–40 kDa.
Heparan sulfate is heparin-like polysaccharide but attached to proteins.
Highest negative-charge density biomolecules
Prevent blood clotting by activating protease inhibitor antithrombin
Binding to various cells regulates development and formation of blood vessels.
Can also bind to viruses and bacteria and decrease their virulence

61. FIGURE 27-7 Molecular basis for heparan sulfate enhancement of the binding of thrombin to antithrombin. In this crystal structure of thrombin, antithrombin, and a 16 residue heparan-sulfate-like polymer, all crystallized together, the binding sites for heparan sulfate in both proteins are rich in Arg and Lys residues. These positively charged regions, shown in blue, allow strong electrostatic interaction with multiple negatively charged sulfates and carboxylates of the heparan sulfate. Consequently, the affinity of antithrombin for thrombin is three orders of magnitude greater in the presence of heparan sulfate than in its absence. Regions of thrombin and antithrombin rich in negatively charged residues are shown in red in this electrostatic representation
of the two proteins.

62. Structures and Roles of Some Polysaccharides
TABLE 7-2
Structures and Roles of Some Polysaccharides
Primer
Typea
Repeating unitb
Size (number of monosaccharide units)
Roles/significance
Starch
Energy storage: in plants
Amylose
Amylopectin
Homo-
(α1S4) Glc, linear
(α1S4) Glc, with (α1S6) Glc branches every 24–30 residues
50–5,000
Up to 106
Glycogen
(α1S4) Glc, with (α1S6) Glc branches every 8–12 residues
Up to 50,000
Energy storage: in bacteria and animal cells
Cellulose
(β1S4) Glc
Up to 15,000
Structural: in plants, gives rigidity and strength to cell walls
Chitin
(β1S4) GlcNAc
Very large
Structural: in insects, spiders, crustaceans, gives rigidity and strength to exoskeletons
Dextran
(α1S6) Glc, with (α1S3) branches
Wide range
Structural: in bacteria, extracellular adhesive
Peptidoglycan
Hetero-; peptides attached
4)Mur2Ac(β1S4) GlcNAc(β1
Structural: in bacteria, gives rigidity and strength to cell envelope
Agarose
Hetero-
3)D-Gal (β1S4)3,6- anhydro-L-Gal(α1
1,000
Structural: in algae, cell wall material
Hyaluronan (a glycosaminoglycan)
Hetero-; acidic
4)GlcA (β1S3) GlcNAc(β1
Up to 100,000
Structural: in vertebrates, extracellular matrix of skin and connective tissue; viscosity and lubrication in joints
aEach polymer is classified as a homopolysaccharide (homo-) or heteropolysaccharide (hetero-).
bThe abbreviated names for the peptidoglycan, agarose, and hyaluronan repeating units indicate that the polymer contains repeats of this disaccharide unit. For example, in peptidoglycan, the GlcNAc of one disaccharide unit is (β1S4)-linked to the first residue of the next disaccharide unit.

63. Glycoconjugates: Glycoprotein
A protein with small oligosaccharides attached
Carbohydrate ia attached via its anomeric carbon to amino acids on the protein.
Common connections occur at Ser, Thr, and Asn.
About half of mammalian proteins are glycoproteins.
Only some bacteria glycosylate a few of their proteins.
Carbohydrates play role in protein-protein recognition.
Viral proteins are heavily glycosylated; this helps evade the immune system.

64. FIGURE 7-30 Oligosaccharide linkages in glycoproteins
FIGURE 7-30 Oligosaccharide linkages in glycoproteins. (a) O-linked oligosaccharides have a glycosidic bond to the hydroxyl group of Ser or Thr residues (light red), illustrated here with GalNAc as the sugar at the reducing end of the oligosaccharide. One simple chain and one complex chain are shown. (b) N-linked oligosaccharides have an N-glycosyl bond to the amide nitrogen of an Asn residue (green), illustrated here with GlcNAc as the terminal sugar. Three common types of oligosaccharide chains that are N-linked in glycoproteins are shown. A complete description of oligosaccharide structure requires specification of the position and stereochemistry (α or β) of each glycosidic linkage.

65. Glycoconjugates: Glycolipids
Lipids with covalently bound oligosaccharide
They are parts of plant and animal cell membranes.
In vertebrates, ganglioside carbohydrate composition determines blood groups.
In gram-negative bacteria, lipopolysaccharides cover the peptidoglycan layer.

66. FIGURE 7-31 Bacterial lipopolysaccharides
FIGURE 7-31 Bacterial lipopolysaccharides. Schematic diagram of the lipopolysaccharide of the outer membrane of Salmonella typhimurium. Kdo is 3-deoxy-D-manno-octulosonic acid (previously called ketodeoxyoctonic acid); Hep is L-glycero-D-manno-heptose; AbeOAc is abequose (a 3,6-dideoxyhexose) acetylated on one of its hydroxyls. There are six fatty acid residues in the lipid A portion of the molecule. Different bacterial species have subtly different lipopolysaccharide structures, but they have in common a lipid region (lipid A), a core oligosaccharide also known as endotoxin, and an “O-specific” chain, which is the principal determinant of the serotype (immunological reactivity) of the bacterium. The outer membranes of the gram-negative bacteria S. typhimurium and E. coli contain so many lipopolysaccharide molecules that the cell surface is virtually covered with O-specific chains.

67. Glycoconjugates: Proteoglycans
Sulfated glucoseaminoglycans attached to a large rod-shaped protein in cell membrane
syndecans: protein has a single transmembrane domain
glypicans: protein is anchored to a lipid membrane
interact with a variety of receptors from neighboring cells and regulate cell growth

68. FIGURE 7-25a Two families of membrane proteoglycans
FIGURE 7-25a Two families of membrane proteoglycans. (a) Schematic diagrams of a syndecan and a glypican in the plasma membrane. Syndecans are held in the membrane by hydrophobic interactions between a sequence of nonpolar amino acid residues and plasma membrane lipids; they can be released by a single proteolytic cut near the membrane surface. In a typical syndecan, the extracellular amino-terminal domain is covalently attached (by tetrasaccharide linkers such as those in Fig. 7–24) to three heparan sulfate chains and two chondroitin sulfate chains. Glypicans are held in the membrane by a covalently attached membrane lipid (GPI anchor; see Fig. 11–13), but are shed if the bond between the lipid portion of the GPI anchor (phosphatidylinositol) and the oligosaccharide linked to the protein is cleaved by a phospholipase. All glypicans have 14 conserved Cys residues, which form disulfide bonds to stabilize the protein moiety, and either two or three glycosaminoglycan chains attached near the carboxyl terminus, close to the membrane surface.

69. FIGURE 7-25b Two families of membrane proteoglycans
FIGURE 7-25b Two families of membrane proteoglycans. (b) Along a heparan sulfate chain, regions rich in sulfated sugars, the NS domains (green), alternate with regions with chiefly unmodified residues of GlcNAc and GlcA, the NA domains (gray). One of the NS domains is shown in more detail, revealing a high density of modified residues: GlcNS (N-sulfoglucosamine), with a sulfate ester at C-6; and both GlcA and IdoA, with a sulfate ester at C-2. The exact pattern of sulfation in the NS domain differs among proteoglycans.

70. Proteoglycans
Different glycosaminoglycans are linked to the core protein.
Linkage from anomeric carbon of xylose to serine hydroxyl
Our tissues have many different core proteins; aggrecan is the best studied.

71. FIGURE 7-24 Proteoglycan structure, showing the tetrasaccharide bridge
FIGURE 7-24 Proteoglycan structure, showing the tetrasaccharide bridge. A typical tetrasaccharide linker (blue) connects a glycosaminoglycan—in this case chondroitin 4-sulfate (orange)—to a Ser residue in the core protein. The xylose residue at the reducing end of the linker is joined by its anomeric carbon to the hydroxyl of the Ser residue.

72. Proteoglycan Aggregates
Hyaluronan and aggrecan form huge (Mr > 2 • 108) noncovalent aggregates.
They hold a lot of water (1000 its weight) and provide lubrication.
Very low friction material
Covers joint surfaces: articular cartilage
reduced friction
load balancing

73. FIGURE 7-28 Proteoglycan aggregate of the extracellular matrix
FIGURE 7-28 Proteoglycan aggregate of the extracellular matrix. Schematic drawing of a proteoglycan with many aggrecan molecules. One very long molecule of hyaluronan is associated noncovalently with about 100 molecules of the core protein aggrecan. Each aggrecan molecule contains many covalently bound chondroitin sulfate and keratan sulfate chains. Link proteins at the junction between each core protein and the hyaluronan backbone mediate the core protein–hyaluronan interaction. The micrograph shows a single molecule of aggrecan, viewed with the atomic force microscope (see Box 19–2).

74. Extracellular Matrix (ECM)
Material outside the cell
Strength, elasticity, and physical barrier in tissues
Main components
proteoglycan aggregates
collagen fibers
elastin (a fibrous protein)
ECM is a barrier for tumor cells seeking to invade new tissues.
Some tumor cells secrete heparinase that degrades ECM.

75. Interaction of the Cells with ECM
Some integral membrane proteins are proteoglycans.
syndecans
Other integral membrane proteins are receptors for extracellular proteoglycans.
integrins
These proteins link cellular cytoskeleton to the ECM and transmit signals into the cell to regulate:
cell growth
cell mobility
apoptosis
wound healing

76. FIGURE 7-29 Interactions between cells and the extracellular matrix
FIGURE 7-29 Interactions between cells and the extracellular matrix. The association between cells and the proteoglycan of the extracellular matrix is mediated by a membrane protein (integrin) and by an extracellular protein (fibronectin in this example) with binding sites for both integrin and the proteoglycan. Note the close association of collagen fibers with the fibronectin and proteoglycan.

77. Oligosaccharides in Recognition
FIGURE 7-37 Role of oligosaccharides in recognition events at the cell surface and in the endomembrane system. (a) Oligosaccharides with unique structures (represented as strings of hexagons) are components of a variety of glycoproteins or glycolipids on the outer surface of plasma membranes. Their oligosaccharide moieties are bound by extracellular lectins with high specificity and affinity. (b) Viruses that infect animal cells, such as the influenza virus, bind to cell surface glycoproteins as the first step in infection. (c) Bacterial toxins, such as the cholera and pertussis toxins, bind to a surface glycolipid before entering a cell. (d) Some bacteria, such as H. pylori, adhere to and then colonize or infect animal cells. (e) Selectins (lectins) in the plasma membrane of certain cells mediate cell-cell interactions, such as those of leukocytes with the endothelial cells of the capillary wall at an infection site. (f) The mannose 6-phosphate receptor/lectin of the trans Golgi complex binds to the oligosaccharide of lysosomal enzymes, targeting them for transfer into the lysosome.

78. Glycoconjugates: Analysis
FIGURE 7-39 Separation and quantification of the oligosaccharides in a group of glycoproteins. In this experiment, the mixture of proteins extracted from kidney tissue was treated to release oligosaccharides from glycoproteins, and the oligosaccharides were analyzed by matrixassisted laser desorption/ionization mass spectrometry (MALDI MS). Each distinct oligosaccharide produces a peak at its molecular mass, and the area under the curve reflects the quantity of that oligosaccharide. The most prominent oligosaccharide here (mass u) is composed of 13 sugar residues; other oligosaccharides, containing as few as 7 and as many as 19 residues, were also resolved by this method.

79. Chapter 7: Summary In this chapter, we learned about:
structures of some important monosaccharides
structures and properties of disaccharides
structures and biological roles of polysaccharides
functions of glycosylaminoglycans as structural components of the extracellular matrix
functions glycoconjugates in regulating a variety of biological functions