Sugars and Polysaccharides

March 24, 2015

Sugars and Polysaccharides•  Carbohydrates or Saccharides are the most

abundant class of biological molecules.•  General formula (C•H2O)n where n≥3. •  Monosaccharides are basic building blocks.•  Oligosaccharides: a few covalently linked

monosaccharides.•  Polysaccharides: many covalently linked

monosaccharides.!

Major Carbohydrate Classes•  Monosaccharides

–  Single polyhydroxy aldehyde or ketone units•  Oligosaccharides

–  Short chains of monosaccharides, <20–  Most abundant are the disaccharides–  Most oligosaccharides of 3 or more units are joined

to nonsugar molecules•  Polysaccharides

–  Contain more than 20 monosaccharide units–  Many contain hundreds or thousands of

monosaccharides–  May be in linear (cellulose) or branched (glycogen)

chains

Monosaccharides•  Consist of aldehydes or ketones with one or more

hydroxyl groups.•  Identified based on the nature of the carbonyl group:

–  Aldehyde -> aldose–  Ketone -> ketose

•  Further classified based on the number of carbon atoms.–  3 -> trioses–  4 -> tetroses–  5 -> pentoses–  Etc…

•  Often contain multiple chiral centers.–  D sugars have the same configuration as does D-glyceraldehyde

at the asymmetric center farthest from the carbonyl group. [Fischer Convention]

–  Aldoses generally have 2n-2 stereoisomers.!

CH2OH

CHOH OH

HO CH2OH

CHOH

CH2OH

CHOH OH

D-Glyceraldehyde D-Glyceraldehyde

CH2OH

CHOHO H

H CH2OH

CHOHO

CH2OH

CHOHO H

L-Glyceraldehyde L-Glyceraldehyde

Fischer Projections and Stereochemistry

R

S

Monosaccharide Stereoisomers

•  The L sugars are the mirror images of their D isomer counterparts.

•  Epimers are stereoisomers that differ only in their configuration at one chiral carbon atom.!

CH2OH

H OH

H OH

HO H

H OH

CHO

CH2OH

HO H

HO H

H OH

HO H

CHO

CH2OH

H OH

H OH

HO H

H OH

CHO

CH2OH

H OH

H OH

HO H

HO H

CHO

D-Glucose L-Glucose

D-mannoseD-Glucose

D isomer L isomer

Epimers

Enantiomers

Aldoses: Stereochemical RelationshipsCCHO

CH2OHH OH

CCHO

CH OH

CH2OHH OH

CCHO

CHO H

CH2OHH OH

D-Glyceraldehyde

D-Erythrose D-Threose

CC

CHO H

CH2OHH OH

CC

CHO H

CH2OHH OH

CC

CH OH

CH2OHH OH

CC

CH OH

CH2OHH OH

CHO CHO CHO CHOHO HH OHHO HH OH

D-Ribose (Rib) D-Arabinose (Ara) D-Xylose (Xyl) D-Lyxose (Lyx)

CC

CHO H

CH2OHH OH

CH OH

CC

CHO H

CH2OHH OH

CH OH

CC

CHO H

CH2OHH OH

CHO H

CC

CHO H

CH2OHH OH

CHO H

CC

CH OH

CH2OHH OH

CHO H

CC

CH OH

CH2OHH OH

CHO H

CC

CH OH

CH2OHH OH

CH OH

CC

CH OH

CH2OHH OH

CH OH

CHO CHOHOH OH

CHOCHOCHOCHOCHOCHOH HO H HO H HOH OH H OH H OH H

D-Allose D-Altrose D-Mannose (Man)

D-Gulose D-Idose D-Galactose (Gal)

D-TaloseD-Glucose (Glc)

Aldopentoses

Aldotetroses

Aldotriose

Aldohexoses

Ketoses: Stereochemical Relationships

•  Ketoses have one less chiral center than their aldose counterparts.

•  Ketoses have 2n-3 stereoisomers (n = number of carbon atoms).

•  Ketoses with the carbonyl at the C2 position are most prevalent.

•  Nomenclature: insert -ul- before the -ose ending in the name of the corresponding aldose.

CH2OHCCH2OH

O

Dihydroxyacetone

CCCH2OH

O

CH2OHH OH

D-Erythrulose

CCCH2OH

O

CH OH

CH2OHOHH

CCCH2OH

O

CHO H

CH2OHOHH

D-Ribulose D-Xylulose

CCCH2OH

O

CH OH

COHH

CH2OHOHH

CCCH2OH

O

CHO H

COHH

CH2OHOHH

CCCH2OH

O

CH OH

CHHO

CH2OHOHH

CCCH2OH

O

CHO H

CHHO

CH2OHOHH

D-Sorbose D-TagatoseD-Psicose D-Fructose

Configurations and Conformations•  Aldehydes and ketones

can react with alcohols to form hemiacetals and hemiketals respectively.

•  Aldehydes/ketones of monosaccharides can react with hydroxyl groups intramolecularly to form cyclic hemiacetals/hemiketals.

•  Haworth projection formulas.!

CH2OHCCC

H OHH OH

HO HCH OHC

O H

OH

OH

CH2OH

HO

H

H

OH

OH

H1

2

3

4

5

6

61

2

34

5OH

HO

CH2OH

H

H

OH H

OHOH

H

CH2OHCCC

H OHH OH

HO HC OCH2OH

2

3

4

5

6

1

OH O CH2OHHOCH2

OHHH

OH

HO

H

HOCH2

HOH

OH

H

OCH2OH

D-Glucoseα-D-Glucopyranose

α-D-FructofuranoseD-Fructose

Cyclic Sugars•  6-membered rings:

pyranoses.•  5-membered rings:

furanoses.•  Anomers differ in

configuration at the hemiacetal or hemiketal carbon.

•  This carbon is called the anomeric carbon.!

•  Anomers: α and β isomers.!

Pyran

Furan

O

O OH

HO

CH2OH

H

H

OH H

OHOH

H

O CH2OHHOCH2

OHHH

OH

HO

H

α-D-Glucopyranose

α-D-Fructoruranose

OH

HO

CH2OH

H

H

OH H

OHOH

H

α-D-Glucopyranose

anomeric carbon

OH

HO

CH2OH

H

H

OH H

OHH

OH

β-D-Glucopyranose

Anomers

Fischer -> Haworth•  Haworth projections used to

represent cyclic saccharide structures.

•  Substituents extend either above or below the ring.–  Substituents on the left in a

Fischer projection are drawn above the ring.

–  Substituents on the right in a Fischer projection are drawn below the ring.

–  Exception: the carbon whose hydroxyl group forms the hemiacetal/hemiketal. !

–  Remember α- and β-configurations. !

CH2OHCCC

H OHH OH

HO HCH OHC

O H

2

3

4

5

6

1

OH

HO

CH2OH

H

H

OH H

OHOH

H

CH2OHCCC

H OHH OH

HO HC OCH2OH

2

3

4

5

6

1

O CH2OHHOCH2

OHHH

OH

HO

H

D-Glucoseα-D-Glucopyranose

α-D-FructoruranoseD-Fructose

Fischer Projection Haworth Projection

Anomers and Interconversion•  Anomers are defined based on the relative position of the

OH group on the anomeric carbon.!α - OH on the opposite side of the ring from the CH2OH.β - OH on the same side of the ring from the CH2OH.

•  Monosaccharide anomers in solution interconvert readily.•  Interconvesion proceeds via the linear form.!

OH

HO

CH2OH

H

H

OH H

OHOH

H

α-D-Glucopyranose

OH

HO

CH2OH

H

H

OH H

OHH

OH

β-D-GlucopyranoseCH2OHCH OHCH OHCHO HCH OHC

H O

D-Glucose

Conformational Variability•  Pyranoses can assume

boat and chair conformations.

•  Ring conformation effects chemical reactivity.–  Equatorial OH

groups esterify more readily than axial OH groups.

•  Furanose rings have similar conformational variability.

•  Substituents influence conformational preferences.!

OH

HO

H

HO

H

HOHH OH

OH

O

OH

H

OH

H

OH

OHH

HH

HO

a

e

a

e

a

aea

e

e

ae

Possible chair confomrations for β-D-glucopyranose

Boat Chair

Pyranoses

Furanoses

Glycosidic Bonds

•  Glycosidic bonds are formed by the condensation of the anomeric OH and another OH group (or in the case of nucleosides, N).

•  Formation of glycosidic bonds is acid catalyzed.•  Glycosidic bonds link sugar monomers in di- and

polysaccharides.!

OH

HO

CH2OH

H

H

OH H

OHOH

H

α-D-Glucopyranose

OH

HO

CH2OH

H

H

OH H

OHOCH3

H OH

HO

CH2OH

H

H

OH H

OHH

OCH3

+ CH3OHH+

Methyl−α-D-Glucoside Methyl−β-D-Glucoside

Oxidation and Reduction•  Aldehydes of aldoses can be

oxidized to carboxylic acids under mild conditions (resulting in aldonic acids).

•  Saccharides bearing anomeric carbons that are not involved in glycosidic bonds are called reducing sugars.

•  Oxidation of the terminal primary alcohol to the carboxylic acid results in uronic acids.

•  Both aldoses and ketoses can be reduced to their alcohols resulting in sugar alcohols.!

CH2OH

HO HH OHH OH

HO H

H O

D-Mannose

CH2OH

HO HH OHH OH

HO H

HO O

D-Mannic acid

CH2OH

HO HH OHH OH

HO HCH2OH

Mannitol

CO2H

HO HH OHH OH

HO H

H O

D-Mannuronic Acid

Oxidation Oxidation

Reduction

Sugar Derivatives•  In deoxy sugars, an -OH

group has been replaced with and H.

•  In amino sugars, one or more OH groups have been replaced with amino groups or acetylated amino groups.

•  Amino sugars are common components in polysaccharides.!

O OHHOCH2

HHH

OH

H

OH

β-Ribose

O OHHOCH2

HHH

OH

H

H

β-2-Deoxyribose

OH

HO

CH2OH

H

H

OH H

OHOH

H

α-D-Glucose

OH

HO

CH2OH

H

H

OH H

NH2

OH

H

α-D-Glucosamine

OH

HO

CH2OH

H

H

OH H

HN

OH

H

N-Acetyl-α-D-Glucosamine

OCH3

Intro to Polysaccharides•  Most carbohydrates in nature are

polysaccharides.•  Have four characteristics:

–  Identity of monosaccharide units– Length of chains– Types of bonds linking units– Degree of branching in chains

Polysaccharides!•  Polysaccharides (glycans): monosaccharides linked

together by glycosidic bonds.•  Homopolysaccharides are composed of one type of

monosaccharide.•  Heteropolysaccharides are composed of more than

one type of monosaccharide. Their composition is usually repetitive.

•  Polysaccharides are not limited to linear construction. They can be branched.

•  Exoglycosidases and endoglycosidases: enzymes that cleave glycosidic bonds. !

Disaccharides!

•  Disaccharides are two monosaccharides joined by an O-glycosidic bond.

•  The reaction generally involves the anomeric carbon.

•  They end with a free anomeric carbon is the reducing end.

•  Few tri- or higher oligosaccharides.

O HHOCH2

CH2OHH

OH

HO

HGlucose Fructose

OH

HO

CH2OH

H

H

OH H

OH

H

Oα β1

2 3

1

2

3

Sucrose

OHO

H

CH2OH

H

H

OH H

OHH

OHCH2OH

H

H

OH H

OHOH

H

O

GlucoseGalactose

β1 4

Lactose

OH

HO

CH2OH

H

H

OH H

OH

H OHCH2OH

H

H

OH H

OHOH

H

Glucose

α1 4

Glucose

O

Maltose

Naming of Disaccharides•  Anomeric configuration of left

monosaccharide is given first.•  Nonreducing residue is named,

including furanosyl or pyranosyl.•  The two carbons in the glycosidic

bond are identified: (1! 4), (1->6) etc.

•  The second residue is named.–  Sucrose : O-α-D-glucopyranosyl-(1-

>2)-β-D-fructofuranoside [note -ide ending].

–  Lactose : O-β-D-galactopyranosyl-(1->4)-D-glucopyranose.

O HHOCH2

CH2OHH

OH

HO

HGlucose Fructose

OH

HO

CH2OH

H

H

OH H

OH

H

Oα β1

2 3

1

2

3

Sucrose

OHO

H

CH2OH

H

H

OH H

OHH

OHCH2OH

H

H

OH H

OHOH

H

O

GlucoseGalactose

β1 4

Lactose

OH

HO

CH2OH

H

H

OH H

OH

H OHCH2OH

H

H

OH H

OHOH

H

Glucose

α1 4

Glucose

O

Maltose

Polysaccharides!•  Structural Polysaccharides:

Cellulose and Chitin.•  Cellulose is the primary

component of plant cell walls. •  Linear polymer of D-glucose.•  Linkages, β(1->4).•  Up to 15,000 saccharide

units.•  Extensive interstrand

hydrogen bonding.•  Accounts for almost half the

carbon in the biosphere.!

OHCH2OH

H

H

OH H

OHH

OHCH2OH

H

H

OH H

OHH

β1 4

Glucose

O

nGlucose

Cellulose

OHCH2OH

H

H

OH H

HNH

OHCH2OH

H

H

OH H

HNH

β1 4O O

n

N-Acetylglucosamine

Chitin

OCH3

OCH3

N-Acetylglucosamine

Structural Polysaccharides!•  Structural Polysaccharides:

Cellulose and Chitin.•  Chitin is the primary

component of invertebrate exoskeletons.

•  Almost as abundant as cellulose.

•  Linear homopolymer of N-acetyl-D-glucosamine.

•  Linkages, β(1->4).•  Structure is similar to that of

cellulose.

OHCH2OH

H

H

OH H

OHH

OHCH2OH

H

H

OH H

OHH

β1 4

Glucose

O

nGlucose

Cellulose

OHCH2OH

H

H

OH H

HNH

OHCH2OH

H

H

OH H

HNH

β1 4O O

n

N-Acetylglucosamine

Chitin

OCH3

OCH3

N-Acetylglucosamine

Storage Polysaccharides!•  Starch: storage in plants.•  Mixture of glycans:

–  The linear homopolymer α-amylose (1->4).

–  The branched homopolymer amylopectin (1->4) and (1->6).

–  Amylopectin molecules can be as large as 106 glucose residues.

•  Glycogen: storage in animals.–  Resembles amylopectin.–  More highly branched.!

OHCH2OH

H

H

OH H

OH

H OHCH2OH

H

H

OH H

OH

H

α1 4

Glucose

O

n

OHCH2OH

H

H

OH H

OH

H4

O Oα α1 1

OHCH2OH

H

H

OH H

OH

H OHCH2

H

H

OH H

OH

H

α1 4

Glucose

O

n

OHCH2OH

H

H

OH H

OH

H4

O Oα α1 1

OHCH2OH

H

H

OH H

HOO

H4

Oα1

6

α-Amylose (1->4 linkages)

OHCH2OH

H

H

OH H

OH

H4

Oα1

Amylopectin (1->4 linkages, 1->6 branches every 24-30 residues.)Glycogen (1->4 linkages, 1->6 branches every 8-12 residues.)

Glycosaminoglycans!•  Glycosaminoglycans =

mucopolysaccharides.•  Primary component of

ground substance, gel-like matrix.

•  Extracellular spaces contain collagen and elastin fibres embedded in ground substance.

•  Linear polysaccharides consisting of alternating uronic acid and hexosamine.

•  Solutions are viscous and demonstrate elasticity.!

OH

HO

CH2OH

H

H

H

HNH

4β1

OHCO2

-

H

H

OH H

OHH

4O β

1

D-Glucuronate

N-Acetyl-D-glucosamine

O O

OCH3

Hyaluronate (hyaluronan)

O-O3SO

H

CH2OH

H

H

H

HNH

4β1

OHCO2

-

H

H

OH H

OHH

4O β

1

D-Glucuronate

N-Acetyl-D-galactosamine-4-sulfate

O O

OCH3

Chondroitin-4-sulfateComponent of cartiledge and connective tissues

Important component of ground substance, synovial fluid and vitrious humor of the eye. (also in bacterial capsules)

OHH

CO2-

H

OH H

OSO3-

H

OHCH2OSO3

-

H

H

OH H

NHOSO3-

H

α1 4O

Oα

L-Iduronate-2-sulfate

N-Sulfo-D-glucosamine-6-sulfate

HeparinVariably sulfated, most negaive polyelectrolyte in mammalian tissues. Inhibits blood clotting.