Principles of BIOCHEMISTRY Third Edition HORTON MORAN Prentice

Principles of BIOCHEMISTRY Third Edition HORTON MORAN Prentice Hall c 2002 OCHS Chapter 8 RAWN SCRIMGEOUR 1

Chapter 8 - Carbohydrates • Carbohydrates (“hydrate of carbon”) have empirical formulas of (CH 2 O)n , where n ≥ 3 • Monosaccharides one monomeric unit • Oligosaccharides ~2 -20 monosaccharides • Polysaccharides > 20 monosaccharides • Glycoconjugates linked to proteins or lipids Prentice Hall c 2002 Chapter 8 2

8. 1 Most Monosaccharides are Chiral Compounds • Aldoses - polyhydroxy aldehydes • Ketoses - polyhydroxy ketones • Most oxidized carbon: aldoses C-1, ketoses usually C-2 • Trioses (3 carbon sugars) are the smallest monsaccharides Prentice Hall c 2002 Chapter 8 3

Aldoses and ketoses • Aldehyde C-1 is drawn at the top of a Fischer projection • Glyceraldehyde (aldotriose) is chiral (C-2 carbon has 4 different groups attached to it) • Dihydroxyacetone (ketotriose) does not have an asymmetric or chiral carbon and is not a chiral compound Prentice Hall c 2002 Chapter 8 4

Fig 8. 1 Fischer projections of: (a) L- and Dglyceraldehyde, (b) dihydroxyacetone Prentice Hall c 2002 Chapter 8 5

Fig 8. 2 Stereo view of L- and D-glyceraldehyde (L) Prentice Hall c 2002 (D) Chapter 8 6

Fig 8. 3 Fisher projections of 3 to 6 carbon D-aldoses • D-sugars have the same configuration as D-glyceraldehyde in their chiral carbon most distant from the carbonyl carbon • Aldoses shown in blue (next slide) are most important in biochemistry Prentice Hall c 2002 Chapter 8 7

Fig. 8. 3 Prentice Hall c 2002 Chapter 8 8

Fig. 8. 3 (continued) Prentice Hall c 2002 Chapter 8 9

Fig 8. 3 (continued) Prentice Hall c 2002 Chapter 8 10

Enantiomers and epimers • D-Sugars predominate in nature • Enantiomers - pairs of D-sugars and L-sugars • Epimers - sugars that differ at only one of several chiral centers • Example: D-galactose is an epimer of D-glucose at C-4 Prentice Hall c 2002 Chapter 8 11

Fig 8. 4 Fisher projections of L- and D-glucose Prentice Hall c 2002 Chapter 8 12

Fig 8. 5 Fisher projections of the 3 to 6 carbon D-ketoses (blue structures are most common) Prentice Hall c 2002 Chapter 8 13

Fig. 8. 5 (continued) Prentice Hall c 2002 Chapter 8 14

Fig 8. 5 (continued) Prentice Hall c 2002 Chapter 8 15

8. 2 Cyclization of Aldoses and Ketoses Fig. 8. 6 Reaction of an alcohol with: (a) An aldehyde to form a hemiacetal (b) A ketone to form a hemiketal Prentice Hall c 2002 Chapter 8 16

Fig 8. 7 (a) Pyran and (b) furan ring systems • (a) Six-membered sugar ring is a “pyranose” • (b) Five-membered sugar ring is a “furanose” Prentice Hall c 2002 Chapter 8 17

Fig 8. 8 Cyclization of D-glucose to form glycopyranose • Fischer projection (top left) • Three-dimensional figure (top right) • C-5 hydroxyl close to aldehylde group (lower left) Prentice Hall c 2002 Chapter 8 18

Fig. 8. 8 (continued) • Reaction of C-5 hydroxyl with one side of C-1 gives a, reaction with the other side gives b Prentice Hall c 2002 Chapter 8 19

Fig 8. 9 Cyclization of D-ribose to form a- and b-D-ribopyranose and a- and b-D-ribofuranose Continued on next slide Prentice Hall c 2002 Chapter 8 20

Fig. 8. 9 (continued) Continued next slide Prentice Hall c 2002 Chapter 8 21

Fig 8. 9 (continued) Prentice Hall c 2002 Chapter 8 22

8. 3 Conformations of Monosaccharides Fig. 8. 10 Conformations of b-D-ribofuranose Prentice Hall c 2002 Chapter 8 23

Fig 8. 11 Conformations of b-D-glucopyranose Haworth projection Chair conformation Boat conformation (b) Stereo view of chair (left), boat (right) Prentice Hall c 2002 Chapter 8 24

Fig 8. 12 Conformations of b-D-glucopyranose • Top conformer is more stable because it has the bulky hydroxyl substituents in equatorial positions (less steric strain) Prentice Hall c 2002 Chapter 8 25

8. 4 Derivatives of Monosaccharides • Many sugar derivatives are found in biological systems • Some are part of monosaccharides, oligosaccharides or polysaccharides • These include sugar phosphates, deoxy and amino sugars, sugar alcohols and acids Prentice Hall c 2002 Chapter 8 26

Table 8. 1 Prentice Hall c 2002 Chapter 8 27

A. Sugar Phosphates Fig 8. 13 Some important sugar phosphates Prentice Hall c 2002 Chapter 8 28

B. Deoxy Sugars • In deoxy sugars an H replaces an OH Fig 8. 14 Deoxy sugars Prentice Hall c 2002 Chapter 8 29

C. Amino Sugars • An amino group replaces a monosaccharide OH • Amino group is sometimes acetylated • Amino sugars of glucose and galactose occur commonly in glycoconjugates Prentice Hall c 2002 Chapter 8 30

Fig 8. 15 Several amino sugars • Amino and acetylamino groups are shown in red Prentice Hall c 2002 Chapter 8 31

Fig. 8. 15 (continued) Prentice Hall c 2002 Chapter 8 32

D. Sugar Alcohols (polyhydroxy alcohols) • Sugar alcohols: carbonyl oxygen is reduced Fig 8. 16 Several sugar alcohols Prentice Hall c 2002 Chapter 8 33

E. Sugar Acids • Sugar acids are carboxylic acids • Produced from aldoses by: (1) Oxidation of C-1 to yield an aldonic acid (2) Oxidation of the highest-numbered carbon to an alduronic acid Prentice Hall c 2002 Chapter 8 34

Fig 8. 17 Sugar acids derived from glucose Prentice Hall c 2002 Chapter 8 35

Fig. 8. 17 (continued) Prentice Hall c 2002 Chapter 8 36

F. Ascorbic Acid (Vitamin C) • L-Ascorbic acid is derived from D-glucuronate Fig 8. 18 L-Ascorbic acid Prentice Hall c 2002 Chapter 8 37

8. 5 Disaccharides and Other Glycosides • Glycosidic bond - primary structural linkage in all polymers of monosaccharides • An acetal linkage - the anomeric sugar carbon is condensed with an alcohol, amine or thiol • Glucosides - glucose provides the anomeric carbon Prentice Hall c 2002 Chapter 8 38

Fig 8. 19 Glucopyranose + methanol yields a glycoside Prentice Hall c 2002 Chapter 8 39

A. Structures of Disaccharides Fig 8. 20 Structures of (a) maltose, (b) cellobiose Prentice Hall c 2002 Chapter 8 40

Fig. 8. 20 (continued) Structures of (c) lactose, (d) sucrose Prentice Hall c 2002 Chapter 8 41

B. Reducing and Nonreducing Sugars • Monosaccharides and most disaccharides are hemiacetals (contain a reactive carbonyl group) • Called reducing sugars because they can reduce metal ions (Cu 2+, Ag+) • Examples: glucose, maltose, cellobiose, lactose Prentice Hall c 2002 Chapter 8 42

C. Nucleosides and Other Glycosides • Anomeric carbons of sugars can form glycosidic linkages with alcohols, amines and thiols • Aglycones are the groups attached to the anomeric sugar carbon • N-Glycosides - nucleosides attached via a ring nitrogen in a glycosidic linkage Prentice Hall c 2002 Chapter 8 43

Fig 8. 21 Structures of three glycosides Prentice Hall c 2002 Chapter 8 44

8. 6 Polysaccharides • Homoglycans - homopolysaccharides containing only one type of monosaccharide • Heteroglycans - heteropolysaccharides containing residues of more than one type of monosaccharide • Lengths and compositions of a polysaccharide may vary within a population of these molecules Prentice Hall c 2002 Chapter 8 45

Prentice Hall c 2002 Chapter 8 46

A. Starch and Glycogen • D-Glucose is stored intracellularly in polymeric forms • Plants and fungi - starch • Animals - glycogen • Starch is a mixture of amylose (unbranched) and amylopectin (branched) Prentice Hall c 2002 Chapter 8 47

Fig 8. 22 Structure of amylose (a) Amylose is a linear polymer (b) Assumes a left-handed helical conformation in water Prentice Hall c 2002 Chapter 8 48

Fig 8. 23 Structure of amylopectin Prentice Hall c 2002 Chapter 8 49

Fig 8. 24 Action of a- and b-amylase on amylopectin • a-Amylase cleaves random internal a-(1 -4) glucosidic bonds • b-Amylase acts on nonreducing ends Prentice Hall c 2002 Chapter 8 50

B. Cellulose and Chitin Fig 8. 25 Structure of cellulose (a) Chair conformation (b) Haworth projection Prentice Hall c 2002 Chapter 8 51

Fig 8. 26 Stereo view of cellulose fibrils • Intra- and interchain H-bonding gives strength Prentice Hall c 2002 Chapter 8 52

Fig 8. 27 Structure of chitin • Repeating units of b-(1 -4)Glc. NAc residues Prentice Hall c 2002 Chapter 8 53

8. 7 Glycoconjugates • Heteroglycans appear in three types of glycoconjugates: Proteoglycans Peptidoglycans Glycoproteins Prentice Hall c 2002 Chapter 8 54

A. Proteoglycans • Proteoglycans - glycosaminoglycan-protein complexes • Glycosaminoglycans - unbranched heteroglycans of repeating disaccharides (many sulfated hydroxyl and amino groups) • Disaccharide components include: (1) amino sugar (D-galactosamine or D-glucosamine), (2) an alduronic acid Prentice Hall c 2002 Chapter 8 55

Fig 8. 28 Repeating disaccharide of hyaluronic acid • Glc. UA = D-glucuronate • Glc. NAc= N-acetylglucosamine Prentice Hall c 2002 Chapter 8 56

Fig 8. 29 Proteoglycan aggregate of cartilage Prentice Hall c 2002 Chapter 8 57

B. Peptidoglycans • Peptidoglycans - heteroglycan chains linked to peptides • Major component of bacterial cell walls • Heteroglycan composed of alternating Glc. NAc and N-acetylmuramic acid (Mur. NAc) • b-(1 4) linkages connect the units Prentice Hall c 2002 Chapter 8 58

Fig 8. 30 Glycan moiety of peptidoglycan Prentice Hall c 2002 Chapter 8 59

Fig 8. 31 Structure of the peptidoglycan of S. aureus (a) Repeating disaccharide unit, (b) Cross-linking of the peptidoglycan macromolecule (to tetrapeptide, next slide) Prentice Hall c 2002 Chapter 8 60

Fig. 8. 31 (continued) (to disaccharide, previous slide) Prentice Hall c 2002 Chapter 8 61

Penicillin inhibits a transpeptidase involved in bacterial cell wall formation • Fig 8. 32 Structures of penicillin and -D-Ala • Penicillin structure resembling -D-Ala is shown in red Prentice Hall c 2002 Chapter 8 62

C. Glycoproteins • Proteins that contain covalently-bound oligosaccharides • O-Glycosidic and N-glycosidic linkages • Oligosaccharide chains exhibit great variability in sugar sequence and composition • Glycoforms - proteins with identical amino acid sequences but different oligosaccharide chain composition Prentice Hall c 2002 Chapter 8 63

Four subclasses of O-glycosidic linkages (1) Gal. NAc-Ser/Thr (most common) (2) 5 -Hydroxylysine (Hyl) to D-galactose (unique to collagen) (3) Gal-Xyl-Ser-core protein (4) Glc. NAc to a single serine or threonine Prentice Hall c 2002 Chapter 8 64