Principles of BIOCHEMISTRY Third Edition

Prentice Hall c2002 Chapter 8 1

Principles ofPrinciples of BIOCHEMISTRYBIOCHEMISTRYThird EditionThird Edition

HORTON MORAN OCHS RAWN SCRIMGEOUR

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Chapter 8 - Carbohydrates

• Carbohydrates (“hydrate of carbon”) have empirical formulas of (CH2O)n , where n ≥ 3

• Monosaccharides one monomeric unit

• Oligosaccharides ~2-20 monosaccharides

• Polysaccharides > 20 monosaccharides

• Glycoconjugates linked to proteins or lipids

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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

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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

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Fig 8.1 Fischer projections of: (a) L- and D-glyceraldehyde, (b) dihydroxyacetone

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Fig 8.2 Stereo view of L- and D-glyceraldehyde

(L) (D)

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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

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Fig. 8.3

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Fig. 8.3 (continued)

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Fig 8.3 (continued)

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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

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Fig 8.4 Fisher projections of L- and D-glucose

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Fig 8.5 Fisher projections of the 3 to 6 carbon D-ketoses (blue structures are most common)

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Fig. 8.5 (continued)

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Fig 8.5 (continued)

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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

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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”

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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)

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Fig. 8.8 (continued)

• Reaction of C-5 hydroxyl with one side of C-1 gives , reaction with the other side gives

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Fig 8.9 Cyclization of D-ribose to form - and -D-ribopyranose and - and -D-ribofuranose

Continued on next slide

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Fig. 8.9 (continued)

Continued next slide

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Fig 8.9 (continued)

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8.3 Conformations of Monosaccharides

Fig. 8.10 Conformations of -D-ribofuranose

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Fig 8.11 Conformations of -D-glucopyranose

(b) Stereo view of chair (left), boat (right)

Haworth projection Chair conformation

Boat conformation

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Fig 8.12 Conformations of -D-glucopyranose

• Top conformer is more stable because it has the bulky hydroxyl substituents in equatorial positions (less steric strain)

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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

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Table 8.1

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A. Sugar Phosphates

Fig 8.13 Some important sugar phosphates

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B. Deoxy Sugars

• In deoxy sugars an H replaces an OH

Fig 8.14 Deoxy sugars

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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

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Fig 8.15 Several amino sugars

• Amino and acetylamino groups are shown in red

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Fig. 8.15 (continued)

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D. Sugar Alcohols (polyhydroxy alcohols)

• Sugar alcohols: carbonyl oxygen is reduced

Fig 8.16 Several sugar alcohols

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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

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Fig 8.17 Sugar acids derived from glucose

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Fig. 8.17 (continued)

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F. Ascorbic Acid (Vitamin C)

• L-Ascorbic acid is derived from D-glucuronate

Fig 8.18 L-Ascorbic acid

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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

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Fig 8.19 Glucopyranose + methanol yields a glycoside

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A. Structures of Disaccharides

Fig 8.20 Structures of (a) maltose, (b) cellobiose

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Fig. 8.20 (continued)

Structures of (c) lactose, (d) sucrose

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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 (Cu2+, Ag+)

• Examples: glucose, maltose, cellobiose, lactose

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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

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Fig 8.21 Structures of three glycosides

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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

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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)

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Fig 8.22 Structure of amylose

(a) Amylose is a linear polymer

(b) Assumes a left-handed helical conformation in water

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Fig 8.23 Structure of amylopectin

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Fig 8.24 Action of - and -amylase on amylopectin

• -Amylase cleaves random internal -(1-4) glucosidic bonds

• -Amylase acts on nonreducing ends

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B. Cellulose and Chitin

Fig 8.25 Structure of cellulose

(a) Chair conformation

(b) Haworth projection

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Fig 8.26 Stereo view of cellulose fibrils

• Intra- and interchain H-bonding gives strength

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Fig 8.27 Structure of chitin

• Repeating units of -(1-4)GlcNAc residues

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8.7 Glycoconjugates

• Heteroglycans appear in three types of glycoconjugates:

Proteoglycans

Peptidoglycans

Glycoproteins

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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

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Fig 8.28 Repeating disaccharide of hyaluronic acid

• GlcUA =D-glucuronate

• GlcNAc= N-acetylglucosamine

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Fig 8.29 Proteoglycan aggregate of cartilage

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B. Peptidoglycans

• Peptidoglycans - heteroglycan chains linked to peptides

• Major component of bacterial cell walls

• Heteroglycan composed of alternating GlcNAc and N-acetylmuramic acid (MurNAc)

• -(1 4) linkages connect the units

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Fig 8.30 Glycan moiety of peptidoglycan

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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)

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Fig. 8.31 (continued)

(to disaccharide, previous slide)

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Penicillin inhibits a transpeptidase involved in bacterial cell wall formation

• Fig 8.32 Structures of penicillin and -D-Ala-D-Ala

• Penicillin structure resembling -D-Ala-D-Ala is shown in red

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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

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Four subclasses of O-glycosidic linkages

(1) GalNAc-Ser/Thr (most common)

(2) 5-Hydroxylysine (Hyl) to D-galactose (unique to collagen)

(3) Gal-Gal-Xyl-Ser-core protein

(4) GlcNAc to a single serine or threonine

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Fig. 8.33 O-Glycosidic and N-glycosidic linkages

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Fig 8.34 Four subclasses of O-glycosidic linkages

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Fig 8.35 Structures of N-linked oligosaccharides

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Fig. 8.35 (continued)